Kinase crystal structures

ABSTRACT

Disclosed are mutants of protein kinase B/Akt which can be crystallised in an enzymatically active conformation, crystals of these mutants and X-ray coordinate data for the crystals. Also disclosed are methods of using the coordinate data provided for identification of modulators of protein kinase activity and for structural analysis of other protein kinases, in particular AGC kinases.

FIELD OF THE INVENTION

[0001] The present invention relates to the enzyme protein kinase B (PKB/Akt), and in particular its crystal structure and the use of this structure in drug discovery.

BACKGROUND TO THE INVENTION

[0002] Protein kinase B (PKB/Akt) is a component of an intracellular signalling pathway of fundamental importance that functions to exert the effects of growth and survival factors, and which mediates the response to insulin and inflammatory signals (Datta et al., 1999; Brazil and Hemmings, 2001). The enzyme is rapidly activated by phosphorylation following stimulation of phosphoinositide 3-kinase, and generation of the lipid second messenger phosphatidylinositol 3,4,5 trisphosphate [PtdIns(3,4,5) P₃]. Activation of PKB occurs by a multi-step mechanism. PKB is first recruited to the membrane by association with PtdIns(3,4,5) P₃ mediated by its N-terminal pleckstrin homology domain in a process that also induces a conformational change of the protein. In this state, PKB is a substrate for phosphorylation at two regulatory sites by membrane-localised kinases (Meier et al. 1997). PDK1 phosphorylates PKB on a Thr residue (Thr-308 of PKBα, Thr-309 of PKBβ, Thr-305 of PKBγ) within the activation segment, stimulating its activity by 30-fold (Alessi et al., 1996a; 1997). A distinct kinase activity, termed PDK2, phosphorylates PKB at a Ser residue of a C-terminal hydrophobic motif (Ser 473 of PKBα, Ser-474 of PKBβ, Ser-472 of PKBγ). Phosphorylation of Ser-474 promotes a 7-10-fold stimulation (Alessi et al., 1996a), which is synergistic with pThr-309 so that phosphorylation of both sites results in an ˜300-fold elevation of protein kinase activity. Whereas PDK1 is well characterised, the identity of PDK2 (also designated Ser-473 Kinase) remains controversial.

[0003] Activated PKB phosphorylates numerous cytosolic and nuclear proteins to regulate cell metabolism, growth and survival. In the insulin signalling pathway, PKB phosphorylates GSK-3, PFK2 and mTOR, inducing glycogenesis and protein synthesis, and regulates glucose uptake by promoting the translocation of Glut4 to the plasma membrane. Cell survival and transformation are controlled by phosphorylation of BAD, caspase-9, forkhead transcription factors and IκB kinase, promoting proliferation and suppressing cell apoptosis (Datta et al., 1999). A mechanism by which PKB stimulates cell cycle progression is by phosphorylation of the CDK inhibitors p21^(WAFl) and p27^(KiP1), causing their retention in the cytoplasm (Zhou et al., 2001), whereas in contrast, PKB mediates nuclear localisation of mdm2 and subsequent regulation of the mdm2/p53 pathway (Mayo and Donner, 2001). In humans, the three isoforms of PKB are highly conserved, with a mean sequence identity of 73%, and share the same regulatory phosphorylation sites. However, a splice variant of PKBγ lacks the C-terminal regulatory phosphorylation site, and interestingly, the specific activity of this splice variant, isolated from stimulated cells, is ˜10-fold lower than the full length γ isoform, a value which is consistent with the role of the C-terminal phosphorylation site to stimulate PKB activity (Brodbeck et al., 2001). CTMP is a negative regulator of PKBα, which by binding to the C-terminal region of the protein, suppresses phosphorylation of Thr-308 and Ser-473 (Maira et al., 2001).

[0004] PKB plays an important role in the generation of human malignancy. The enzyme is the cellular homologue of v-Akt, an oncogene of the transforming murine leukaemia virus AKT8 isolated from a mouse lymphoma (Staal et al., 1977). Viral-Akt is a fusion of the viral Gag protein with the PKBα sequence (Bellacosa et al., 1991). Myristoylation of the Gag sequence targets v-Akt to the cell membrane, resulting in its constitutive phosphorylation. The genes for the α and β isoforms of PKB are over-expressed and amplified in ovarian, prostate, pancreatic, gastric, and breast tumours (Testa and Bellacosa, 2001). Compelling evidence linking PKB to oncogenesis stems from the elucidation of the mechanism of the PTEN tumour suppressor gene. PTEN is one of the most commonly mutated genes in human cancer and somatic deletions or mutations of PTEN have been identified in glioblastomas, melanoma and prostate cancers, and are associated with increased susceptibility to breast and thyroid tumours (Cantley and Neel, 1999). PTEN negatively regulates the PI-3 kinase/PKB pathway by dephosphorylating PtdIns(3,4,5)P₃ on the D-3 position, and therefore loss of PTEN activity leads to a constitutive cell survival stimulus (Maehama and Dixon., 1998; Myers et al., 1998).

[0005] Protein kinase B is a member of the AGC-family of serine/threonine specific protein kinases that also includes PKA, PKC, PDK1 and the p70 and p90 S6-kinases (Coffer and Woodgett, 1991; Jones et al., 1991a). As well as being structurally related, AGC-protein kinases share numerous functional similarities such as activation in response to second messengers and dependence on phosphorylation for activity. Members of the family are phosphorylated on a conserved Thr-residue within their activation segment. In vitro PDK1 is capable of phosphorylating AGC-kinases on this position (Vanhaesebroeck and Alessi, 2000), although recent studies using PDK1 deficient ES cells suggest that PDK1 activity is only necessary for PKB and a subset of other AGC-kinases (Williams et al., 2000). The site of C-terminal regulatory phosphorylation of PKB (Ser-474) is within a hydrophobic activation sequence motif (F-x-x-F-[S/T]-Y), conserved within a large proportion of AGC-kinases (Keranen et al., 1995; Pearson et al., 1995). In PKB, substitution of Ser-474 with Asp mimics Ser-474 phosphorylation (Alessi et al., 1996a), and significantly, some a typical PKC isoforms and PRK2 (PKC related kinase-2) have Asp or Glu residues at this position. PKA requires phosphorylation of the activation segment Thr residue (Thr-197) for activity (Yonemoto et al., 1997), although this is a constitutive site of phosphorylation, and unlike other AGC-kinases, is resistant to dephosphorylation by protein phosphatases (Shoji et al., 1979). The hydrophobic motif of PKA is also unusual and comprises the sequence -Phe-Thr-Glu-Phe-350, with Phe-350 corresponding to the C-terminus of the PKA catalytic subunit, and therefore the enzyme lacks a site of regulatory phosphorylation. In the structure of PKA, the motif lies within a surface groove formed in the N-terminal lobe, with the side-chains of the two Phe-residues buried deep into the groove (Knighton et al., 1991a,b; Bossemeyer et al., 1993). Other AGC-kinases are likely to have an equivalent groove, and for PDK1, the groove is thought to allow recognition of specific target kinase substrates via their phosphorylated regulatory segment sequences, although this interaction has been suggested not to be essential for phosphorylation of PKB by PDK1 (Biondi et al., 2000; 2001).

[0006] In order to understand the mechanism of activation of PKB by phosphorylation, and as a framework for the rational development of modulators of PKB activity, knowledge of a PKB protein structure would be extremely valuable. Such knowledge would significantly assist the rational design of novel therapeutics for, e.g. the treatment of diabetes, cancer, neurodegeneration and erectile dysfunction, based on PKB modulators.

[0007] Definitions

[0008] In the following by “binding site” we mean a site (such as an atom, a functional group of an amino acid residue or a plurality of such atoms and/or groups) in a PKB binding cavity which may bind to an agent compound such as a candidate modulator (e.g. inhibitor). Depending on the particular molecule in the cavity, sites may exhibit attractive or repulsive binding interactions, brought about by charge, steric considerations and the like.

[0009] By “AGC kinase” is meant any protein kinase comprising a sequence which has a sequence identity of equal to or greater than 35% at the amino acid level with residues 37-350 of the catalytic subunit of PKA (Shoji et al., 1983). Determination of percentage sequence identity may be performed with the AMPS package as described by Barton (1994). AGC kinases are also described in detail by Hanks and Hunter, FASEB J. (1995) 9: 576, and Hardie, G. and Hanks, S. (eds) The Protein Kinase Facts Book—Protein-Serine Kinases (1995) Academic Press Ltd., London).

[0010] By “fitting”, is meant determining by manual, automatic, or semi-automatic means, interactions between one or more atoms of an agent molecule and one or more atoms or binding sites of the PKB, and calculating the extent to which such interactions are stable. Various computer-based methods for fitting are described further herein.

[0011] By “root mean square deviation” we mean the square root of the arithmetic mean of the squares of the deviations from the mean.

[0012] By a “computer system” we mean the hardware means, software means and data storage means used to analyse atomic coordinate data. The minimum hardware means of the computer-based systems of the present invention comprises a central processing unit (CPU), input means, output means and data storage means. Desirably a monitor is provided to visualise structure data. The data storage means may be RAM or means for accessing computer readable media of the invention. Examples of such systems are microcomputer workstations available from Silicon Graphics Incorporated and Sun Microsystems running Unix based, Windows NT or IBM OS/2 operating systems.

[0013] By “computer readable media” we mean any media which can be read and accessed directly by a computer e.g. so that the media is suitable for use in the above-mentioned computer system. Such media include, but are not limited to: magnetic storage media such as floppy discs, hard disc storage medium and magnetic tape; optical storage media such as optical discs or CD-ROM; electrical storage media such as RAM and ROM; and hybrids of these categories such as magnetic/optical storage media.

DISCLOSURE OF THE INVENTION

[0014] The present invention is at least partly based on overcoming several technical hurdles: the present inventors have (i) produced PKBβ crystals of suitable quality for performing X-ray diffraction analyses, (ii) collected X-ray diffraction data from the crystals, (iii) determined the three-dimensional structure of PKBβ, and (iv) identified binding sites on the enzyme which are likely to be involved in the enzymatic reaction.

[0015] In order to understand the nature of the mechanism of regulation of PKB by PIP₃, the N-terminal PH domain and phosphorylation of the regulatory Thr and Ser phosphorylation sites, the present inventors have generated Sf9/baculovirus expression systems for full length PKBα, PKBβ, PKBγ and PDK1 and also a number of modified forms of the three PKB isoforms. They have succeeded in generating crystal structures for both inactive and active conformations of the enzyme.

[0016] Limited trypsinolysis of full length PKBβ purified from Sf9 cells led to the identification of a protease resistant domain with an N-terminus at Lys-146, which we refer to as ΔPH-PKB. Lys-146 is located within the structurally diverse region linking the pleckstrin homology (PH) and kinase domains of PKB, close to the N-terminus of the corresponding β1-strand of PKA. During the course of the purification, partial cleavage of a C-terminal 3 kDa fragment was observed, suggesting conformational flexibility at the C-terminus of the protein. Human PKBα, PKBβ and PKBγ sequences are structurally diverse within a 12 residue region C-terminal to the conserved PP(D/E) motif (residues 452-454 of PKBP), preceding the C-terminal hydrophobic motif, and corresponding to the C-terminus of the PKBγ splice variant. Using this information, the present inventors constructed a number of new PKB baculovirus Fastbac entry vectors for the generation of PKB insect cell/baculovirus expression systems, and expressed the α and β-isoforms of PKB as the kinase domain, with an N-terminus at Lys-146 (i.e. lacking the PH domain), with and without the C-terminal 21 residues that includes the hydrophobic regulatory segment. These two kinase domains are termed ΔPH-PKB and ΔPH-PKB-ΔC, respectively.

[0017] Thus, using this limited proteolysis, the inventors have defined a stable, compact, crystallisable domain of PKB. The systems used express high levels of protein, that the inventors have purified to homogeneity. Moreover, the inventors have expressed PDK1 using the insect cell/baculovirus system and MAPKAPK2 in the E. coli expression system to enable phosphorylation of PKBβ on Thr309 and Ser474, respectively.

[0018] To prepare defined phosphorylated states of PKB, phosphorylation and dephosphorylation reactions were performed using PDK1(for pThr-309) and the non-specific λ-protein phosphatase, respectively. Distinct phosphorylated states of the protein were resolved using hydrophobic interaction chromatography.

[0019] The phosphorylation state of the protein was analysed by Western blots using phospho-specific antibodies, and the stoichiometry and sites of phosphorylation were quantitatively assessed by mass spectroscopic analysis of trypsin-generated peptides of the protein.

[0020] The inventors have succeeded in the expression, purification, crystallisation and structure determination of three forms of PKBβ in the inactive conformation, which differ in their state of phosphorylation.

[0021] The three crystal forms of human PKBβ are; (i) pΔPH-PKB-ΔC (residues 146 to 460, phosphorylated in vitro on Thr-309), (ii) ΔPH-PKB-ΔC(residues 146 to 460, not phosphorylated on Thr-309), and (iii) ΔPH-PKBβ (residues 146 to 481, dephosphorylated in vitro).

[0022] Two batches of crystals were prepared for crystal form (i), i.e. pΔPH-PKB-ΔC. Summaries of coordinate data, having different resolutions, are provided for each of these crystals (Table 1 below). Thus, data are provided for four crystals in total.

[0023] All four inactive crystals of PKB belong to the same space group and have similar cell dimensions. Summary data for the higher resolution pΔPH-PKB-ΔC crystal, as well as the ΔPH-PKB-ΔC and ΔPH-PKB crystals are shown in Table 1.

[0024] The two crystal preparations of pΔPH-PKB-ΔC diffract to 2.8 and 2.3 Å resolution, when exposed to synchrotron radiation, whereas ΔPH-PKB-ΔC and ΔPH-PKB diffract to 2.7 Å and 2.5 Å respectively.

[0025] The structure of PKB was solved by means of molecular replacement using the ternary complex of mouse PKA (Knighton et al., 1991) as a search object. During initial stages of the refinement, the relative orientations of the N- and C-terminal lobes of the kinase domain were refined, prior to atomic positional refinement (Table 1).

[0026] The resultant structures are believed to provide important insights into the structure activity relationships in the full length PKBβ and its highly homologous isoforms (see Brodbeck et al. 1999). For brevity, as used herein, unless the context demands otherwise, the term PKB is used to encompass full or part-length molecules of any of the three isoforms, which may not or may be phosphorylated e.g. ‘PKBβ’ encompasses the full length PKBβ molecule or a truncated form such as ΔPH-PKBβ (residues 146-481) or ΔPH-PKBβ-ΔC (residues 146-460).

[0027] The present inventors have also produced PKBβ crystals in which PKBβ has adopted an active conformation. This has been achieved by use of two PKBβ constructs based on ΔPH-PKB; one has a S to D mutation at position 474 (designated PKB S474D) while the other (designated PKB-PIF) is a fusion protein comprising residues 146 to 467 of human PKBβ fused to 15 residues from the C terminus of PRK2.

[0028] Each was crystallised as a ternary complex with the nucleotide analogue AMP-PNP and a substrate peptide.

[0029] In general aspects, the present invention is concerned with identifying or obtaining agent compounds for modulating PKB activity, and in preferred embodiments identifying or obtaining actual agent compounds which are inhibitors or activators. Where, methods of identifying or modelling inhibitors are described hereinafter, the skilled person will appreciate that the processes may be applied analogously to other modulators such as activators.

[0030] Crystal structure information presented herein is useful in designing potential modulators and modelling them or their potential interaction with PKB binding cavities, for example, the PKB substrate binding cavity, ATP binding site, or other region of interest (e.g. the hydrophobic motif, or regulatory phosphorylation sites), preferably the ATP binding site Potential modulators may be brought into contact with PKB to test for ability to interact with the PKB binding cavity. Actual modulators may be identified from among potential modulators synthesized following design and model work performed in silico. A modulator identified using the present invention may be formulated into a composition, for instance a composition comprising a pharmaceutically acceptable excipient, and may be used in the manufacture of a medicament for use in a method of treatment. These and other aspects and embodiments of the present invention are discussed below.

[0031] The present invention provides a crystal of PKBβ having a tetragonal space group P2₁2₁2₁, and unit cell dimensions of a=44.94 Å, b=61.00 Å, c=131.32 Å, and more generally a=44.94±0.5 Å, b=61.00±0.5 Å, c=131.32±0.5 Å, preferably a=44.94±0.2 Å, b=61.00±0.2 Å, c=131.32±0.2 Å.

[0032] Alternatively, or additionally, the crystal may have the three dimensional atomic coordinates of Tables 6 or 7. An advantageous feature of the structural data according to Tables 6 and 7 are that they have a high resolution of about 1.6 Å and 1.7 Å respectively.

[0033] Indeed a further aspect of the invention includes within its scope a crystal of protein kinase Bβ (PKBβ) defined by structural data having a resolution of about 1.6 Å.

[0034] The crystallised PKBβ molecules may comprise a mutation corresponding to the mutation S474D in human PKBβ. Additionally or alternatively, the PKBβ may be a fusion protein having a C-terminal tail derived from another AGC kinase, preferably PRK-2. Preferably the C-terminal tail comprises the sequence EEQEMFRDFDYIADW.

[0035] The crystal may comprise the relevant enzyme molecules complexed with either a substrate or substrate analogue, or a nucleotide or nucleotide analogue, or both. The substrate or substrate analogue may be a peptide, for example the GSK-3 peptide described in the Examples below or any suitable substrate as described e.g. in Lawlor and Alessi (2001) (see particularly Table 1) or Manning et al. (2002). The nucleotide or analogue thereof will typically be ATP, or preferably a non-hydrolysable analogue thereof, such as AMP-PNP or ATP-gammaS.

[0036] The coordinates of Tables 6 and 7 provide a measure of atomic location in Angstroms. The coordinates are a relative set of positions that define a shape in three dimensions, so the skilled person would understand that an entirely different set of coordinates having a different origin and/or axes could define a similar or identical shape. Furthermore, the skilled person would understand that varying the relative atomic positions of the atoms of the structure so that the root mean square deviation of the residue backbone atoms (i.e. the nitrogen-carbon-carbon backbone atoms of the protein amino acid residues) is less than 1.5 Å (preferably less than 1.0 Å and more preferably less than 0.5 Å) when superimposed on the coordinates provided for the residue backbone atoms, will generally result in a structure which is substantially the same as the structure of Tables 6 and 7 in terms of both its structural characteristics and usefulness for structure-based analysis, including design of PKBβ modulators.

[0037] Likewise the skilled person would understand that changing the number and/or positions of the water molecules in these structures (where shown) will not generally affect the usefulness of the structure for structure-based analysis. Thus for the purposes described herein as being aspects of the present invention, it is within the scope of the invention if: the coordinates are transposed to a different origin and/or axes; the relative atomic positions of the atoms of the structure are varied so that the root mean square deviation of residue backbone atoms is less than 1.5 Å (preferably less than 1.0 Å and more preferably less than 0.5 Å) when superimposed on the coordinates provided in Tables 6 and 7 for the residue backbone atoms. Reference herein to the coordinate data of Tables 6 and 7 thus includes the coordinate data in which one or more individual values of the Tables are varied in this way.

[0038] Modifications in the native PKBβ crystal structure due to e.g mutations, additions, substitutions, and/or deletions of amino acid residues could lead to variations in the PKBβ atomic coordinates and where such modified forms of PKBβ are being investigated, atomic coordinate data of PKBβ modified so that a ligand that bound to one or more binding sites of PKBβ would be expected to bind to the corresponding binding sites of the modified PKBβ are, for the purposes described herein as being aspects of the present invention, also within the scope of the invention. Reference herein to the coordinates of Tables 6 and 7 thus includes the coordinates modified in this way. Preferably, the modified coordinate data define at least one PKBβ binding site.

[0039] In a further aspect, the invention provides a method for crystallizing a PKB derivative which comprises producing PKB by recombinant production in a host cell, recovering a PKB derivative from the host cell and growing one or more crystals from the recovered PKB derivative, wherein the PKB derivative is a stable protease-resistant form of PKB. The host cell may be of any suitable cell type, for example a eukaryotic cell host, such as a yeast cell, a mammalian cell, or an insect cell. In a preferred embodiment, the host cell is an insect cell, such as an Sf9 cell.

[0040] Typically the derivative lacks all or substantially all of the PH domain. Thus the derivative may be a truncated derivative e.g. truncated to positions 146-460 for PKBβ, or corresponding residues in other isoforms. The derivative may optionally include amino acid residues C-terminal of position 460 in PKBβ or its equivalent, e.g. the C-terminal 21 amino acids of PKBβ. In preferred embodiments the derivative comprises one or more mutations in the C terminal tail, corresponding to the C-terminal 21 amino acids of human PKBβ. Thus the derivative may comprise a mutation corresponding to the mutation S474D in human PKBβ. Additionally or alternatively the derivative may be expressed as a fusion protein with C-terminal residues derived from another AGC kinase such as PRK2 as descibed elsewhere herein.

[0041] The method may further comprise the steps of phosphorylating one or more phosphorylatable residues in vitro with a suitable kinase. For example, PDK1 can be used to phosphorylate Thr-309 in vitro. It has been suggested that MAPKAP 2 kinase can be used to phosphorylate Ser-474 of PKBP/Ser-473 of PKBα (Alessi et al. 1996a). For generation of kinases in the active conformation, the derivative will preferably be phosphorylated at a position corresponding to Thr-309 of human PKBβ.

[0042] Alternatively, the method may comprise the step of dephosphorylation in vitro, to ensure that any adventitious phosphorylation occurring during expression is removed. Numerous suitable enzymes will be known to the skilled person, e.g. the λ protein phosphatase.

[0043] The derivative may be encoded by a vector construct substantially similar to one disclosed herein. The method may include the further step of X-ray diffraction analysis of the obtained crystal.

[0044] Thus, the PKBβ produced by crystallising PKBβ (see the detailed description below) is provided as a crystallised protein suitable for X-ray diffraction analysis.

[0045] The crystal may be grown by any suitable method, e.g. the under oil batch methods as described in the Examples.

[0046] The present invention further provides a recombinant polypeptide comprising the catalytic domain of PKB, the N-terminus of said polypeptide corresponding to Lys-146 of human PKBβ. The polypeptide will typically comprise the full kinase domain which may correspond, for example to amino acid residues 144 to 439 of human PKBα, 146 to 440 of human PKBβ, or 143 to 436 of human PKBγ. In a preferred embodiment the polypeptide comprises amino acids 146 to 460 of human PKBβ, which corresponds to residues 145-459 of PKBα, and 143-456 of PKBγ. It may optionally further comprise the C-terminal region corresponding to amino acids 461 to 481 of human PKBβ or a portion thereof. The recombinant polypeptide may be a mutant or a fusion protein having a mutation equivalent to S474D in human PKBβ and/or be fused to a C-terminal sequence from another AGC kinase. In a preferred embodiment the derivative consists of residues 146 to 467 of human PKBβ fused to the sequence EEQEMFRDFDYIADW.

[0047] Reference to a PKB catalytic domain should be taken to include catalytic domains of mutant PKBs as described below (under ‘Homology Modelling’). The term ‘catalytic domain’ as used herein refers to the structural domain of the protein and should not be interpreted as requiring the polypeptide to have catalytic activity; for example it may contain a mutation which impairs or abrogates activity, e.g. at the active site, but which does not affect the gross structure of the domain.

[0048] The present invention further provides a crystallisable composition comprising a recombinant polypeptide as described above.

[0049] In a further aspect, the present invention provides nucleic acids encoding the polypeptides as described herein. Thus in these nucleic acids, the sequences encoding the catalytic domain are not contiguous with sequences encoding the PH domain of PKB, preferably not contiguous with sequences coding for any amino acids N-terminal of Lys-146.

[0050] The present invention also encompasses a method of making a polypeptide as disclosed, the method including the step of expressing said polypeptide or peptide from nucleic acid encoding it, which in most embodiments will be nucleic acid according to the present invention.

[0051] In another aspect, the invention provides a method of analysing a PKB-ligand complex comprising the step of employing (i) X-ray crystallographic diffraction data from the PKBβ-ligand complex and (ii) a three-dimensional structure of PKBβ to generate a difference Fourier electron density map of the complex, the three-dimensional structure being defined by atomic coordinate data according to Tables 6 and 7. If the PKBβ-ligand complex is crystallised in a different space group to the crystals described herein, molecular replacement methods may be used instead of difference Fourier methods.

[0052] Therefore, in the light of the present disclosure, PKBβ-ligand complexes can be crystallised and analysed using X-ray diffraction methods, e.g. according to the approach described by Greer et al., J. of Medicinal Chemistry, Vol. 37, (1994), 1035-1054, and difference Fourier electron density maps can be calculated based on X-ray diffraction patterns of soaked or co-crystallised PKBβ and the solved structure of un-complexed PKBβ. These maps can then be used to determine whether and where a particular ligand binds to PKBβ and/or changes the conformation of PKBβ.

[0053] Electron density maps can be calculated using programs such as those from the CCP4 computing package (Collaborative Computational Project 4. The CCP4 Suite: Programs for Protein Crystallography, Acta Crystallographica, D50, (1994), 760-763.). For map visualisation and model building programs such as 0 (Jones et al., Acta Crystallography, A47, (1991), 110-119) can be used.

[0054] In another aspect, the invention relates to methods of determining three dimensional structures of target kinases of unknown structure by utilising in whole or in part the structural coordinates provided for PKBβ in any one of the data sets provided herein (Tables 6 and 7).

[0055] The target kinase will typically be homologous to PKB, such as an AGC family kinase (e.g. SGK) (Hanks and Hunter (1995) FASEB J. 9: 576; Hardie, G. and Hanks, S. (eds) The Protein Kinase Facts Book—Protein-Serine Kinases (1995) Academic Press Ltd., London). In particular, it may be an isoform of PKB, such as PKBα or PKBγ. The data provided here relate to the inactive conformation of PKBβ, and so will be useful for determining the structure of the corresponding conformation of other kinases. However, the present invention also extends to the elucidation of the structure of alternative conformations such as active conformations of such target kinases, including PKB, and including the active conformation of PKBβ, or PKB-ligand complexes.

[0056] The primary ways in which the three-dimensional coordinate data of the present invention can be used to solve other target kinase structures are as follows:

[0057] The three-dimensional coordinate data provided herein for PKB may be aligned with an amino acid sequence of a target kinase to match homologous regions of the amino acid sequences, and a structure determined for the target kinase by homology modelling.

[0058] The three-dimensional coordinate data of the present invention may be used to assist in interpretation of a set of raw X-ray crystallographic data obtained for a target kinase, in order to establish a structure for the target kinase.

[0059] Typically, in each of these alternatives, the target structure will be established by the calculation of a set of three-dimensional coordinate data for some or all of the atoms in the target structure.

[0060] Homology Modelling

[0061] Thus the invention provides a method of homology modelling comprising the steps of:

[0062] (a) aligning a representation of an amino acid sequence of a target kinase of unknown structure with the amino acid sequence of PKBβ to match homologous regions of the amino acid sequences;

[0063] (b) modelling the structure of the matched homologous regions of the target kinase on the structure as defined by Tables 6 or 7 of the corresponding regions of PKBβ; and

[0064] (c) determining a conformation (e.g. so that favourable interactions are formed within the target kinase and/or so that a low energy conformation is formed) for the target kinase which substantially preserves the structure of said matched homologous regions.

[0065] The target kinase will typically be a PKB homologue, such as a member of the AGC kinase family. In particular, such a method may be used to determine the structure of the a isoform, γ isoform, or other isoforms of PKB or of related kinases such as the AGC kinase family.

[0066] The term “homologous regions” describes amino acid residues in two sequences that are identical or have similar (e.g. aliphatic, aromatic, polar, negatively charged, or positively charged) side-chain chemical groups. Identical and similar residues in homologous regions are sometimes described as being respectively “invariant” and “conserved” by those skilled in the art.

[0067] Preferably one or all of steps (a) to (c) are performed by computer modelling.

[0068] Homology modelling is a technique that is well known to those skilled in the art (see e.g. Greer, Science, Vol. 228, (1985), 1055, and Blundell et al., Eur. J. Biochem, Vol. 172, (1988), 513). By “homology modelling”, is meant the prediction of related kinase structures based either on x-ray crystallographic data or computer-assisted de novo prediction of structure, based upon manipulation of the coordinate data of Tables 6 or 7.

[0069] The various in silico modelling techniques described in this section and in the other sections of this application may utilize coordinates from any of the crystal data sets provided herein, or from any structure calculated by means of those data sets. To avoid unnecessary repetition, reference is made herein to the coordinate data of Tables 6 and 7.

[0070] “Homology modelling” extends to target kinases, in particular AGC kinases, which are analogues or homologues of the PKB protein whose structure has been determined in the accompanying examples. It also extends to mutants of PKB protein itself.

[0071] In general, comparison of amino acid sequences is accomplished by aligning the amino acid sequence of a polypeptide of a known structure with the amino acid sequence of the polypeptide of unknown structure. Amino acids in the sequences are then compared and groups of amino acids that are homologous are grouped together. This method detects conserved regions of the polypeptides and accounts for amino acid insertions or deletions.

[0072] Homology between amino acid sequences can be determined using commercially available algorithms. The programs BLAST, gapped BLAST, BLASTN, PSI-BLAST and BLAST 2 sequences (provided by the National Center for Biotechnology Information) are widely used in the art for this purpose, and can align homologous regions of two amino acid sequences. These may be used with default parameters to determine the degree of homology between the amino acid sequence of the protein of known structure and other target proteins which are to be modeled.

[0073] Analogues are defined as proteins with similar three-dimensional structures and/or functions and little evidence of a common ancestor at a sequence level.

[0074] Homologues are defined as proteins with evidence of a common ancestor i.e. likely to be the result of evolutionary divergence and are divided into remote, medium and close sub-divisions based on the degree (usually expressed as a percentage) of sequence identity.

[0075] A homologue is defined here as a protein with at least 15% sequence identity or which has at least one functional domain, which is characteristic of PKB, including polymorphic forms of PKB. Typically homologues of PKB will be AGC kinases.

[0076] There are two types of homologue: orthologues and paralogues. Orthologues are defined as homologous genes in different organisms, i.e. the genes share a common ancestor coincident with the speciation event that generated them. Paralogues are defined as homologous genes in the same organism derived from a gene/chromosome/genome duplication, i.e. the common ancestor of the genes occurred since the last speciation event.

[0077] A mutant is a kinase characterized by replacement or deletion of at least one amino acid from a wild type AGC kinase, e.g. PKB. Such a mutant may be prepared for example by site-specific mutagenesis, or incorporation of natural or unnatural amino acids.

[0078] The present invention contemplates “mutants”, and the application of the methods of the present invention to “mutants”, wherein a “mutant” refers to a polypeptide which is obtained by replacing at least one amino acid residue in a native or synthetic ACG kinase with a different amino acid residue and/or by adding and/or deleting amino acid residues within the native polypeptide or at the N- and/or C-terminus of a polypeptide corresponding to a wild-type kinase and which has substantially the same three-dimensional structure as the kinase from which it is derived. By having substantially the same three-dimensional structure is meant having a set of atomic structure co-ordinates that have a root mean square deviation (r.m.s.d.) of less than or equal to about 2.0 Å when superimposed with the atomic structure co-ordinates of the wild-type kinase from which the mutant is derived when at least about 50% to 100% of the C_(α) atoms of the kinase are included in the superposition. A mutant may have, but need not have, enzymatic or catalytic activity.

[0079] To produce homologues or mutants, amino acids present in the said protein can be replaced by other amino acids having similar properties, for example hydrophobicity, hydrophobic moment, antigenicity, propensity to form or break α-helical or β-sheet structures, and so. Substitutional variants of a protein are those in which at least one amino acid in the protein sequence has been removed and a different residue inserted in its place. Amino acid substitutions are typically of single residues but may be clustered depending on functional constraints e.g. at a crystal contact. Preferably amino acid substitutions will comprise conservative amino acid substitutions. Insertional amino acid variants are those in which one or more amino acids are introduced. This can be amino-terminal and/or carboxy-terminal fusion as well as intrasequence. Examples of amino-terminal and/or carboxy-terminal fusions are affinity tags, an MBP tag, and epitope tags.

[0080] Amino acid substitutions, deletions and additions which do not significantly interfere with the three-dimensional structure of the kinase will depend, in part, on the region of the molecule where the substitution, addition or deletion occurs. In highly variable regions of the molecule, non-conservative substitutions as well as conservative substitutions may be tolerated without significantly disrupting the three-dimensional structure of the molecule. In highly conserved regions, or regions containing significant secondary structure, conservative amino acid substitutions are preferred.

[0081] Conservative amino acid substitutions are well-known in the art, and include substitutions made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity and/or the amphipathic nature of the amino acid residues involved. For example, negatively charged amino acids include aspartic acid and glutamic acid; positively charged amino acids include lysine and arginine; amino acids with uncharged polar head groups having similar hydrophilicity values include the following: leucine, isoleucine, valine; glycine, alanine; asparagine, glutamine; serine, threonine; phenylalanine, tyrosine. Other conservative amino acid substitutions are well known in the art.

[0082] In some instances, it may be particularly advantageous or convenient to substitute, delete and/or add amino acid residues to a particular binding site or catalytic residue, in order to provide convenient cloning sites in cDNA encoding the polypeptide, to aid in purification of the polypeptide, etc. Such substitutions, deletions and/or additions which do not substantially alter the three dimensional structure of the wild-type kinase will be apparent to those having skills in the art.

[0083] It should be noted that the mutants contemplated herein need not exhibit enzymatic activity. Indeed, amino acid substitutions, additions or deletions that interfere with the catalytic activity of the kinase but which do not significantly alter the three-dimensional structure of the catalytic region are specifically contemplated by the invention. Such crystalline polypeptides, or the atomic structure co-ordinates obtained therefrom, can be used to identify compounds that bind to the protein.

[0084] Once the amino acid sequences of the polypeptides with known and unknown structures are aligned, the structures of the conserved amino acids in a computer representation of the polypeptide with known structure are transferred to the corresponding amino acids of the polypeptide whose structure is unknown. For example, a tyrosine in the amino acid sequence of known structure may be replaced by a phenylalanine, the corresponding homologous amino acid in the amino acid sequence of unknown structure.

[0085] The structures of amino acids located in non-conserved regions may be assigned manually by using standard peptide geometries or by molecular simulation techniques, such as molecular dynamics. The final step in the process is accomplished by refining the entire structure using molecular dynamics and/or energy minimization.

[0086] Structure Solution

[0087] In a further aspect, the invention provides a method for determining the structure of a target kinase, which method comprises;

[0088] providing the co-ordinates of Tables 6 or 7, and positioning the co-ordinates in the crystal unit cell of said target kinase so as to provide a structure for said target kinase.

[0089] In a preferred aspect of this invention the co-ordinates are used to solve the structure of target kinases particularly homologues of PKB, such as AGC family kinases, including, without limitation, NDR, p70 S6K, p90, PKC, etc.

[0090] The structures of the human PKB provided can be used to solve the crystal structure of other target AGC kinases including other crystal forms of PKB, mutants, and co-complexes of PKB, where X-ray diffraction data of these target proteins has been generated and requires interpretation in order to provide the structure.

[0091] In the case of PKB, this protein may crystallize in more than one crystal form. The structure coordinates of PKB, or portions thereof, as provided by this invention are particularly useful to solve the structure of those other crystal forms of PKB, such as that of the active conformation. They may also be used to solve the structure of PKB mutants or co-complexes, or of the crystalline form of any other protein with significant amino acid sequence homology to any functional domain of PKB, such as an AGC kinase family member.

[0092] In the case of other target proteins, particularly the AGC kinases referred to above, the present invention allows the structures of such targets to be obtained more readily where raw X-ray diffraction data is generated.

[0093] Thus, where X-ray crystallographic or NMR spectroscopic data is provided for a target kinase of unknown three-dimensional structure, the structure of PKB as defined by Tables 6 and 7 may be used to interpret that data to provide a likely structure for the other kinase by techniques which are well known in the art, e.g. phasing in the case of X-ray crystallography and assisting peak assignments in NMR spectra.

[0094] One method that may be employed for these purposes is molecular replacement. In this method, the unknown crystal structure, whether it is another crystal form of PKB, a mutant or co-complex thereof, or the crystal of a target kinase with amino acid sequence homology to any functional domain of PKB, may be determined using any one of the data sets of PKB structure coordinates of this invention as provided herein. This method will provide an accurate structural form for the unknown crystal more quickly and efficiently than attempting to determine such information ab initio.

[0095] Examples of computer programs known in the art for performing molecular replacement are CNX (Brunger A. T.; Adams P. D.; Rice L. M., Current Opinion in Structural Biology, Volume 8, Issue 5, October 1998, Pages 606-611 (also commercially available from Accelerys San Diego, Calif.) or AMORE (Navaza, J. (1994). AMoRe: an automated package for molecular replacement. Acta Cryst. A50, 157-163).

[0096] The invention may also be used to assign peaks of NMR spectra of such proteins, by manipulation of the data provided herein.

[0097] Computer Systems

[0098] In another aspect, the present invention provides systems, particularly a computer system, intended to generate structures and/or perform rational drug design for PKBβ, PKBβ-ligand complexes or PKBβ homologues or mutants, the system containing either (a) atomic coordinate data according to Tables 6 or 7 recorded thereon, said data defining the three-dimensional structure of PKB, or at least selected coordinates thereof; (b) structure factor data for PKB recorded thereon, the structure factor data being derivable from the atomic coordinate data of Tables 6 or 7; (c) a Fourier transform of atomic coordinate data according to Tables 6 or 7, or at least selected coordinates thereof; (d) atomic coordinate data of a target kinase generated by homology modelling of the target based on the data of Tables 6 or 7; (e) atomic coordinate data of a target kinase generated by interpreting X-ray crystallographic data or NMR data by reference to the data of Tables 6 or 7; or (f) structure factor data derivable from the atomic coordinate data of (d) or (e).

[0099] The invention also provides such systems containing atomic coordinate data of target kinases wherein such data has been generated according to the methods of the invention described herein based on the starting data provided by Tables 6 or 7.

[0100] Such data is useful for a number of purposes, including the generation of structures to analyze the mechanisms of action of kinases, and/or to perform rational drug design of compounds which interact with them, such as modulators of kinase activity, e.g. activators or inhibitors.

[0101] In a further aspect, the present invention provides computer readable media with either (a) atomic coordinate data according to either of Tables 6 or 7 recorded thereon, said data defining the three-dimensional structure of PKB, or at least selected coordinates thereof; (b) structure factor data for PKB recorded thereon, the structure factor data being derivable from the atomic coordinate data of Tables 6 or 7; (c) a Fourier transform of atomic coordinate data according to Tables 6 or 7, or at least selected coordinates thereof; (d) atomic coordinate data of a target kinase generated by homology modelling of the target based on the data of Tables 6 or 7; (e) atomic coordinate data of a target kinase generated by interpreting X-ray crystallographic data or NMR data by reference to the data of Tables 6 or 7; or (f) structure factor data derivable from the atomic coordinate data of (d) or (e).

[0102] By providing such computer readable media, the atomic coordinate data can be routinely accessed to model PKB or selected coordinates thereof. For example, RASMOL (Sayle et al., TIBS, Vol. 20, (1995), 374) is a publicly available computer software package which allows access and analysis of atomic coordinate data for structure determination and/or rational drug design.

[0103] On the other hand, structure factor data, which are derivable from atomic coordinate data (see e.g. Blundell et al., in Protein Crystallography, Academic Press, New York, London and San Francisco, (1976)), are particularly useful for calculating e.g. difference Fourier electron density maps.

[0104] Uses of the Structures of the Invention

[0105] In another aspect, the present invention provides methods for modelling the interactions between PKB and modulators of PKB activity. Thus there is provided a method for modelling the interaction between PKB and an agent compound which modulates PKB activity, comprising the steps of:

[0106] (a) employing three-dimensional atomic coordinate data according to either of Tables 6 or 7 to characterise at least one PKBβ binding site;

[0107] (b) providing the structure of said agent compound; and

[0108] (c) fitting said agent compound to the binding site.

[0109] The agent compound may be any compound known to have an effect on PKB activity, such as the peptide activating agents, e.g. PIFtide, described below.

[0110] The present invention further provides a method for identifying an agent compound (e.g. an inhibitor) which modulates PKB (e.g. PKBβ) activity, comprising the steps of:

[0111] (a) employing three-dimensional atomic coordinate data according to Tables 6 or 7 to characterise at least one PKBβ binding site;

[0112] (b) providing the structure of a candidate agent compound;

[0113] (c) fitting the candidate agent compound to the binding sites; and

[0114] (d) selecting the candidate agent compound.

[0115] Preferably a plurality of binding sites are characterised; preferably sufficient binding sites are characterised to define a PKBβ binding cavity and/or the ATP binding site which forms part of the catalytic site.

[0116] For ease of reference, and to avoid unnecessary repetition, only the production of modulators of PKB activity is discussed here. However the present invention is considered to apply equally to the identification of modulators of any target enzyme whose structure has been determined by reference to the three-dimensional coordinate data for PKBβ provided herein. For example, the data provided herein may be used to calculate a structure for a related AGC family kinase, such as (without limitation) SGK, p70 S6K, p90 RSK, PKC, and NDR. Accordingly, the present invention extends to the use of such a structure for identification of modulators of that target enzyme.

[0117] In the inactive conformation of PKBβ, the adenine moiety of ATP is prevented from binding to the ATP binding site by Phe-294. The data presented here show details of the interaction between PKBβ and ATP. Since all known small molecule inhibitors of protein kinases are competitive with ATP, and therefore interact with the ATP binding site, an understanding of the PKB residues involved in the interaction with ATP allows the development of specific and potent inhibitors of this kinase. This information may thus be used to develop potent and specific small molecule inhibitors of PKB in a number of ways PKBβ may be co-crystallised, and/or existing PKBβ crystals may be soaked, for example with known inhibitors of PKB, such as staurosporine, or those discovered in high-throughput screening programmes known to the skilled person.

[0118] Alternatively, or additionally, rational drug design programmes may make full use of the crystallographic coordinates. These techniques are discussed in more detail below.

[0119] It may be desirable to compare the structures of the inactive and active conformations of the enzyme, in order to identify binding sites present on only one of said conformations. The three-dimensional coordinate data for such a site could then be used to identify a ligand capable of binding selectively to, and stabilising, that conformation.

[0120] A plurality (for example two, three or four) of spaced PKBβ binding sites may be characterised and a plurality of respective compounds designed or selected. The agent compound may then be formed by linking the respective compounds into a larger compound which maintains the relative positions and orientations of the respective compounds at the binding sites. The larger compound may be formed as a real molecule or by computer modelling.

[0121] In any event, the determination of the three-dimensional structure of PKBβ provides a basis for the identification of new and specific ligands for PKB e.g. PKBβ, and other members of the AGC family of kinases, e.g. NDR, p70 S6K, p90, PKC, etc., for instance by computer modelling.

[0122] As the structures of Tables 6 and 7 show coordinate data for ternary complexes of the active structures of PKBβ, they may enable the design of competitive inhibitors of PKB, or other AGC kinases, by modelling compounds which compete for the ATP binding site, or the substrate binding site of the kinase.

[0123] Thus the PKBβ binding site may comprise one or more residues implicated in interaction with ATP (or the non-hydrolysable ATP analogue in Tables 6 and 7) in the active conformation of the enzyme.

[0124] Residues making particularly close contacts with AMP-PNP in the structure defined by Table 6 include Val-166, Lys-181, Thr-213, Met-259, Ala-232, Glu-236, Lys-277, Glu-279, Met-282, Thr-292, Asp-293 (Table 3). Thus the binding site may comprise one or more of these residues, or their equivalents in other isoforms of PKB or other AGC kinases.

[0125] Some of these contacts are conserved in PKA, however, there are differences between PKA and PKB. Notably, Thr-213 and Ala-232 are Val in PKA, and Met-282 is Leu in PKA.

[0126] Thus the present invention enables the design of inhibitors of PKB which are selective for PKB over another AGC kinase (e.g. PKA), preferably over a plurality of AGC kinases. That is to say, the candidate agent compound is a better fit to the PKBβ binding site than to a corresponding binding site defined by the corresponding residues of the other kinase. Thus the method may involve the step of comparing the binding of the candidate agent compound to the PKB binding site, and to a corresponding binding site defined by the corresponding residues of the other kinase, e.g. PKA.

[0127] Likewise the structures provided enable the design of candidate agent compounds which are selective for other AGC kinases over PKB, by designing compounds which are a better fit to binding sites on those AGC kinases than to corresponding binding sites on PKB.

[0128] Alternatively, the method may involve the step of comparing the binding of the candidate agent compound to the PKB or AGC kinase binding site, and to a corresponding binding site of a mutant of the same kinase, in which significant residues are changed to those present in the corresponding positions in the other kinase.

[0129] For example, binding may be compared between a PKBβ binding site and a mutant PKBβ binding site having one or more amino acid changes corresponding to mutations T213V, A232V and M282L of human PKBβ.

[0130] The candidate agent compound may be modelled on the non-hydrolysable ATP analogue (AMP-PNP) shown in either of Tables 6 and 7.

[0131] An interaction between a candidate agent compound and a residue of the binding site is considered to mimic an interaction between AMP-PNP and that residue if atoms from the candidate agent compound make similar interactions with corresponding residues in the binding site, e.g. ionic bonds, and electrostatic interactions such as salt bridges, hydrogen bonds, and van der Waals interactions, as well as hydrophobic interactions.

[0132] Preferably the atoms from the candidate agent compound, when fitted to the binding site, lie at a similar distance from atoms of the relevant residue as atoms of AMP-PNP when fitted to the binding site. Distances between atoms of AMP-PNP and atoms of residues in the PKB ATP binding site are shown in Table 3. More generally, an interaction between the candidate agent compound and the binding site may be considered to mimic an interaction between the substrate and the binding site if the relevant atoms have the relevant separations shown in Table 3 +/−1 Å, preferably +/−0.5 Å, more preferably +/−0.2 Å.

[0133] The PKBβ binding site may comprise one or more residues implicated in interaction with the substrate or substrate analogue, e.g. the GSK-3 peptide shown in Tables 6 and 7 in the active configuration of the enzyme.

[0134] Residues making particularly close contacts with the GSK-3 peptide in the structure defined by Tables 6 and 7 include Glu-279, Tyr-316, Glu-342, Glu-236, Glu-279, Phe-310, Cys-311 and Leu-317.

[0135] The candidate binding agent may be modelled on the GSK-3 peptide shown in either of Tables 6 or 7.

[0136] When the candidate agent compound is fitted to the binding site, an interaction between the candidate agent compound and the binding site may mimic an interaction between one or more of the following sets of residues of Tables 6 and 7:

[0137] Arg-4 of GSK-3 and residues Glu-279, Tyr-316, Glu-342 of PKB-PIF;

[0138] Arg-6 of GSK-3 and residues Glu-236, Glu-279 of PKB-PIF;

[0139] Thr-7 of GSK-3 and residues Glu-279 of PKB-PIF;

[0140] Phe-10 of GSK-3 and residues Phe-310, Cys-311, Leu-317 of PKB-PIF;

[0141] Glu-12 of GSK-3 and residues Phe-310 of PKB-PIF.

[0142] An interaction between a candidate agent compound and a residue of the binding site is considered to mimic an interaction between the substrate peptide and that residue if atoms from the candidate agent compound make similar interactions with corresponding residues in the binding site, ionic bonds, and electrostatic interactions such as salt bridges, hydrogen bonds, and van der Waals interactions, as well as hydrophobic interactions.

[0143] Preferably the atoms from the candidate agent compound, when fitted to the binding site, lie at a similar distance from atoms of the relevant residue as atoms of the substrate when fitted to the binding site. Distances between atoms of the substrate and atoms of residues in the substrate binding site are shown in Table 4. More generally, an interaction between the candidate agent compound and the binding site may be considered to mimic an interaction between the substrate and the binding site if the relevant atoms have the relevant separations shown in Table 4 +/−1 Å, preferably +/−0.5 Å, more preferably +/−0.2 Å.

[0144] The structure shown in Table 6 further shows the interactions between the residues of PIFtide and the catalytic domain of PKB. This data may be used to design mimetics of PIFtide for activation of PKB.

[0145] Residues making particularly close contacts with the residues of the PRK-2 activation motif, i.e. the PIF residues in the structure defined by Table 6 include Val-194, Gln-220, Ile-188, Ile-189, Val-198, Arg-202, Gln-205, Ser-201, Ala-218, Leu-225, Phe-227, Arg-208, Leu-215 and Lys-216.

[0146] The candidate binding agent may be modelled on the PIF residues shown in Table 6, and preferably the residues of the activation motif.

[0147] When the candidate agent compound is fitted to the binding site, an interaction between the candidate agent compound and the binding site may mimic an interaction between one or more of the following sets of residues of PKB-PIF shown in Table 6:

[0148] Met-472 and Val-194, Gln-220;

[0149] Phe-473 and Ile-188, Ile-189, Val-194, Val-198;

[0150] Asp-475 and Arg-202, Gln-205;

[0151] Phe-476 and Ser-201, Ala-218, Leu-225, Phe-227;

[0152] Asp-477 and Gln-220;

[0153] Tyr-478 and Arg-208, Leu-215;

[0154] Ala-480 and Lys-216;

[0155] Asp-481 and Arg-208;

[0156] Trp-479 and Leu-215, Lys-216.

[0157] An interaction between a candidate agent compound and a residue of the binding site is considered to mimic an interaction between a PIF residue and that residue if atoms from the candidate agent compound make similar interactions with corresponding residues in the binding site, ionic bonds, and electrostatic interactions such as salt bridges, hydrogen bonds, and van der Waals interactions, as well as hydrophobic interactions.

[0158] Preferably the atoms from the candidate agent compound, when fitted to the binding site, lie at a similar distance from atoms of the relevant residue as atoms of PIF residues when fitted to the binding site. Distances between atoms of PIF residues and atoms of residues in the activation motif binding site are shown in Table 5. More generally, an interaction between the candidate agent compound and the binding site may be considered to mimic an interaction between PIF residues and the binding site if the relevant atoms have the relevant separations shown in Table 5 +/−1 Å, preferably +/−0.5 Å, more preferably +/−0.2 Å.

[0159] The data in Tables 3, 4 and 5 is provided for illustrative purposes only—similar data may be derived by the skilled person directly from the data of Tables 6 and 7. The similarity of the two structures shown in Tables 6 and 7 shows that PKB S474D makes essentially the same interactions with AMP-PNP and GSK-3 as PKB-PIF. The C-terminal tail of PKB S474D makes similar contacts with the catalytic domain as the corresponding residues of PKB-PIF make to the catalytic domain, except that there are no contacts to Met-469, Asp-472, Ile-476 and Trp-479. The skilled person will understand that precise details of the interactions between the C-terminal tail and the catalytic domain of PKB S474D may be derived from Table 7 and used in exactly the same way as the data of Table 5. The present invention encompasses use of all such derived data.

[0160] More specifically, a potential modulator of PKB activity can be examined through the use of computer modelling using a docking program such as GRAM, DOCK, or AUTODOCK (see Walters et al., Drug Discovery Today, Vol.3, No.4, (1998), 160-178, and Dunbrack et al., Folding and Design, 2, (1997), 27-42). This procedure can include computer fitting of candidate inhibitors to PKB to ascertain how well the shape and the chemical structure of the candidate inhibitor will bind to the enzyme.

[0161] Also computer-assisted, manual examination of the binding cavity structure of PKBβ may be performed. The use of programs such as GRID (Goodford, J. Med. Chem., 28, (1985), 849-857)—a program that determines probable interaction sites between molecules with various functional groups and the enzyme surface—may also be used to analyse the binding cavity to predict partial structures of inhibiting compounds.

[0162] Computer programs can be employed to estimate the attraction, repulsion, and steric hindrance of the two binding partners (e.g. the PKBβ and a candidate inhibitor). Generally the tighter the fit, the fewer the steric hindrances, and the greater the attractive forces, the more potent the potential modulator since these properties are consistent with a tighter binding constant. Furthermore, the more specificity in the design of a potential drug, the more likely it is that the drug will not interact with other proteins as well. This will tend to minimise potential side-effects due to unwanted interactions with other proteins

[0163] In one embodiment a plurality of candidate agent compounds are screened or interrogated for interaction with the binding sites. In one example, step (b) involves providing the structures of the candidate agent compounds, each of which is then fitted in step (c) to computationally screen a database of compounds (such as the Cambridge Structural Database) for interaction with the binding sites. In another example, a 3-D descriptor for the agent compound is derived, the descriptor including e.g geometric and functional constraints derived from the architecture and chemical nature of the binding cavity. The descriptor may then be used to interrogate the compound database, the identified agent compound being the compound which matches with the features of the descriptor. In effect, the descriptor is a type of virtual pharmacophore.

[0164] For example, the descriptor may be based on the AMP-PNP molecule which interacts with the ATP binding site, the substrate peptide which interacts with the substrate binding site, or the residues of the C-terminal tail of PKB-PIF, or PKB S474D, which interact with the catalytic domain.

[0165] Having designed or selected possible binding partners, these can then be screened for activity. Consequently, the method preferably comprises the further steps of:

[0166] (e) obtaining or synthesising the candidate agent compound; and

[0167] (f) contacting the candidate agent compound with PKBβ to determine the ability of the candidate agent compound to interact with PKBβ (or similarly with other homologous isoforms or AGC kinase family members).

[0168] In step (f) the candidate agent compound may be contacted with PKBβ in the presence of a substrate, and typically a buffer, to determine the ability of the candidate agent compound to inhibit PKBβ. The buffer will typically contain ATP. The substrate may be e.g. a peptide corresponding to the sequence GRPRTTSFAE, or salts thereof. So, for example, an assay mixture for PKB may be produced which comprises the candidate inhibitor, substrate and buffer

[0169] Instead of, or in addition to, performing e.g. a chemical assay, the method may comprise the further steps of:

[0170] (e) obtaining or synthesising the candidate agent compound;

[0171] (f) forming a complex of PKB and the candidate agent compound; and

[0172] (g) analysing (e.g. by the method of an earlier aspect of the invention) said complex by X-ray crystallography or NMR spectroscopy to determine the ability of the candidate agent compound to interact with PKB.

[0173] Detailed structural information can then be obtained about the binding of the agent compound to PKB, and in the light of this information adjustments can be made to the structure or functionality of the compound, e.g. to improve binding to the binding cavity. Steps (e) to (g) may be repeated and re-repeated as necessary. For X-ray crystallographic analysis, the complex may be formed by crystal soak-in methods or co-crystallisation.

[0174] Greer et al. describes an iterative approach to ligand design based on repeated sequences of computer modelling, protein-ligand complex formation and X-ray crystallographic or NMR spectroscopic analysis. Thus novel thymidylate synthase inhibitor series were designed de novo by Greer et al., and PKB inhibitors may also be designed in the this way. More specifically, using e.g. GRID on the solved 3D structure of PKBβ, a ligand (e.g. a potential inhibitor) for PKB may be designed that complements the functionalities of the PKB binding site(s). The ligand can then be synthesised, formed into a complex with PKB or other AGC family kinase, and the complex then analysed by X-ray crystallography to identify the actual position of the bound ligand. The structure and/or functional groups of the ligand can then be adjusted, if necessary, in view of the results of the X-ray analysis, and the synthesis and analysis sequence repeated until an optimised ligand is obtained. Related approaches to structure-based drug design are also discussed in Bohacek et al., Medicinal Research Reviews, Vol.16, (1996), 3-50.

[0175] As a result of the determination of the PKBβ 3D structure, more purely computational techniques for rational drug design may also be used to design PKB modulators, e.g. activators or inhibitors (for an overview of these techniques see e.g. Walters et al.). For example, automated ligand-receptor docking programs (discussed e.g. by Jones et al. in Current Opinion in Biotechnology, Vol.6, (1995), 652-656) which require accurate information on the atomic coordinates of target receptors may be used to design potential PKB modulators.

[0176] Linked-fragment approaches to drug design also require accurate information on the atomic coordinates of target receptors. The basic idea behind these approaches is to determine (computationally or experimentally) the binding locations of plural ligands to a target molecule, and then construct a molecular scaffold to connect the ligands together in such a way that their relative binding positions are preserved. The connected ligands thus form a potential lead compound that can be further refined using e.g. the iterative technique of Greer et al. For a virtual linked-fragment approach see Verlinde et al., J. of Computer-Aided Molecular Design, 6, (1992), 131-147, and for NMR and X-ray approaches see Shuker et al., Science, 274, (1996), 1531-1534 and Stout et al., Structure, 6, (1998), 839-848. The use of these approaches to design PKB inhibitors is made possible by the determination of the PKBβ structure.

[0177] Many of the techniques and approaches to structure-based drug design described above rely at some stage on X-ray analysis to identify the binding position of a ligand in a ligand-protein complex. A common way of doing this is to perform X-ray crystallography on the complex, produce a difference Fourier electron density map, and associate a particular pattern of electron density with the ligand. However, in order to produce the map (as explained e.g. by Blundell et al.) it is necessary to know beforehand the protein 3D structure (or at least the protein structure factors). Therefore, determination of the PKBβ structure also allows difference Fourier electron density maps of PKB-ligand complexes to be produced, which can greatly assist the process of rational drug design.

[0178] The approaches to structure-based drug design described above all require initial identification of possible compounds for interaction with the target bio-molecule (in this case PKB). Sometimes these compounds are known e.g. from the research literature.

[0179] Thus the present invention provides methods of identifying mimetics of known modulators of PKB activity. The methods may involve the identification of a binding site for the known modulator. Subsequently, candidate compounds may be fitted to the same binding site in order to identify a compound which will mimic the activity of the known modulator.

[0180] For example, the methods described above may be used to model the binding site at which PKB interacts with a known modulator, e.g. an activating agent such as PIFtide, as described elsewhere in this specification. A mimetic of the activating agent may then be designed by fitting candidate compounds to that binding site.

[0181] Thus the methods of the present invention for identifying agent compounds which modulate PKB activity may involve fitting a candidate agent compound to a PKB binding site, wherein the binding site has previously been determined to bind a known agent compound as described above.

[0182] When no suitable known starting compounds are known, or when novel compounds are wanted, a first stage of the drug design program may involve computer-based in silico screening of compound databases (such as the Cambridge Structural Database) with the aim of identifying compounds which interact with the binding site or sites of the target bio-molecule. Screening selection criteria may be based on pharmacokinetic properties such as metabolic stability and toxicity. However, determination of the PKBβ structure allows the architecture and chemical nature of each PKBβ binding site to be identified, which in turn allows the geometric and functional constraints of a descriptor for the potential inhibitor to be derived. The descriptor is, therefore, a type of virtual 3-D pharmacophore, which can also be used as selection criteria or filter for database screening.

[0183] In another aspect, the invention includes a compound which is identified as a modulator of PKB activity by the method of the earlier aspect.

[0184] Following identification of a suitable modulator compound, it may be manufactured and/or used in the preparation, i.e. manufacture or formulation, of a composition such as a medicament, pharmaceutical composition or drug. These may be administered to individuals for treatment of an appropriate condition, e.g. inhibitors for use in the treatment of cancers, or activators in the use of diabetes, erectile dysfunction or neurodegeneration.

[0185] Thus, the present invention extends in various aspects not only to a modulator as provided by the invention, but also a pharmaceutical composition, medicament, drug or other composition comprising such a modulator e.g. for treatment (which may include preventative treatment) of disease such as cancer; a method, comprising administration of such a composition to a patient, e.g. for treatment of disease such as cancer; use of such a modulator in the manufacture of a composition for administration, e.g. for treatment of disease such as cancer; and a method of making a pharmaceutical composition comprising admixing such a modulator with a pharmaceutically acceptable excipient, vehicle or carrier, and optionally other ingredients.

[0186] Although the examples relate to crystals of PKB mutants having an S474D mutation, and a chimera having a C terminus derived from PRK2, it will be clear that any of the peptide or non-peptide activating agents described below may be used to induce the catalytic domain of a kinase to adopt a catalytically active conformation, for crystallisation or for any other purposes. The activating agents may be covalently or non-covalently linked to the catalytic domain of the enzyme, as described below.

[0187] Activation of AGC kinases

[0188] The insights into the mechanism of kinase activation, which the crystal structure of PKB provides, enables the provision of novel methods for activating AGC kinases, and materials for use in those methods.

[0189] The present invention further provides a method of inducing a catalytic domain of an AGC kinase to adopt an active conformation, wherein the AGC kinase in its native form is regulated by phosphorylation of a regulatory phosphorylation site residue in a C-terminal regulatory segment distinct from said catalytic domain, said method comprising the steps of:

[0190] (a) providing a polypeptide comprising said catalytic domain, and

[0191] (b) forming a non-covalent complex between said polypeptide and an activating agent, wherein contact between said activating agent and said catalytic domain induces said catalytic domain to adopt an active conformation.

[0192] The activating agent does not catalyse covalent modification of the polypeptide; in particular, the activating agent is not a kinase and does not phosphorylate the polypeptide. Rather the activating agent interacts with the catalytic domain to induce ordering of the regions of the kinase corresponding to the αB and αC helices and activation segment of PKB. Full activity may also require phosphorylation of a residue in the activation segment corresponding to Thr-309 of human PKBβ. This disorder to order transition forms a hydrophobic surface groove in the N-terminal lobe of the catalytic domain which binds the activating agent. The interaction is believed to be stabilised further by electrostatic interactions between residues of the catalytic domain and one or more negative charges of the activating agent.

[0193] The catalytic domain may be that of any AGC kinase which, in its native form, is regulated by phosphorylation of a regulatory phosphorylation site residue in a C-terminal regulatory segment distinct from the catalytic domain. Such phosphorylation typically activates the kinase. Such kinases include, but are not limited to, PKB, PKC, NDR, SGK, and the p70 and p90 S6-kinases and include variants of these kinases which do not possess the regulatory phosphorylation site, such as the splice variant of PKBγ (Brodbeck et al., 2001). However, they do not include kinases which are not regulated by phosphorylation of this sort, such as PKA, PRK2, and PDK1.

[0194] By “AGC kinase” is meant any protein kinase which has a sequence identity of equal to or greater than 35% at the amino acid level with residues 37-350 of the catalytic subunit of PKA (Shoji et al., 1983). Determination of percentage sequence identity may be performed with the AMPS package as described by Barton (1994). AGC kinases are also described in detail by Hanks and Hunter FASEB J. (1995) 9: 576 and Hardie, G. and Hanks, S. (eds) The Protein Kinase Facts Book—Protein-Serine Kinases (1995) Academic Press Ltd., London).

[0195] Thus the kinases which can be activated by the methods of the present invention possess a regulatory segment distinct from the catalytic domain, which in PKB constitutes the portion of the protein C-terminal of the catalytic domain. Thus the term ‘C-terminal regulatory segment’ signifies only that this portion of the polypeptide is located C-terminal of the catalytic domain, and does not imply that any portion of the regulatory segment need form the C-terminus of the polypeptide. In a preferred embodiment, the C-terminal regulatory segment corresponds to amino acid residues 440 to 480 of PKBβ, 441 to 481 of PKBβ, 438 to 479 of PKBγ, or corresponding residues in other kinases.

[0196] The regulatory segment contains a hydrophobic motif at least four amino acids and typically six amino acid residues in length, which typically contains the sequence FXXF, e.g. FXXFXY/F, although the kinase NDR has the sequence FXXY at this position. Here, and throughout this specification, X represents any amino acid. The regulatory segment further comprises a regulatory phosphorylation site, which typically lies within the hydrophobic motif, e.g. Ser-473 of PKBα, Ser-474 of PKBβ, Ser 472 of PKBγ. For example, PKBα, β and γ all have the sequence FPQFSY within their regulatory segment.

[0197] The term ‘catalytic domain’ as used herein refers to a protein domain which when folded has a particular characteristic structure, and not necessarily to a domain having any particular catalytic activity. Thus the catalytic domain may contain a mutation which impairs or abrogates activity, e.g. substitution or deletion of one or more amino acid residues at the active site, but which does not affect the gross structure of the folded domain.

[0198] The minimum catalytic domain of a given kinase is the minimum polypeptide sequence from that kinase which will fold stably into the appropriate conformation when expressed independently, and may correspond, for example to amino acid residues 144 to 439 of human PKBα, 146 to 440 of human PKBβ, or 143 to 436 of human PKBγ (see

[0199]FIG. 7—all references made herein to numbering of residues of PKBα or β refer to the human PKB sequences as shown in FIG. 7).

[0200] Catalytic domains of other target AGC kinases may be identified by alignment of the target sequences with that of PKBβ.

[0201] In general, comparison of amino acid sequences is accomplished by aligning the amino acid sequence of a polypeptide of a known structure with the amino acid sequence of the polypeptide of unknown structure. Amino acids in the sequences are then compared and groups of amino acids that are homologous are grouped together. This method detects conserved regions of the polypeptides and accounts for amino acid insertions or deletions.

[0202] Homology between amino acid sequences can be determined using commercially available algorithms. The programs BLAST, gapped BLAST, BLASTN, PSI-BLAST and BLAST 2 sequences (provided by the National Center for Biotechnology Information) are widely used in the art for this purpose, and can align homologous regions of two amino acid sequences. These may be used with default parameters to determine the degree of homology between the amino acid sequence of the protein of known structure and those of target proteins.

[0203] The polypeptide may consist solely or essentially of the catalytic domain in isolated form, e.g. a recombinant single domain. Alternatively the polypeptide may contain further domains of the AGC kinase, fusion partners, epitope tags, etc. For example, the catalytic domain may be contiguous with all or part of one or more further domains found in the native wild-type form of the enzyme, such as a pleckstrin homology (PH) domain or the C-terminal regulatory segment of PKB.

[0204] In preferred embodiments, the catalytic domain is from an isoform of PKB, e.g. from the α, β or γ isoforms of PKB.

[0205] The catalytic domain may be provided in phosphorylated form, e.g. in the activation segment of the catalytic domain. For example, in a preferred embodiment the catalytic domain is from PKB and is provided phosphorylated at Thr-308 (PKBα), Thr-309 (PKBβ) or Thr-305 (PKBγ). In alternative embodiments where the catalytic domain is derived from another AGC kinase, it may be phosphorylated at the corresponding position.

[0206] The methods of the present invention may further comprise the steps of phosphorylating one or more phosphorylatable residues of the catalytic domain in vitro with a suitable kinase. For example, PDK1 can be used to phosphorylate Thr-309 in vitro, while it has been suggested that MAPKAP 2 kinase can be used to phosphorylate Ser-474 (Alessi et al., 1996a).

[0207] Additionally or alternatively, the methods of the present invention may comprise the step of dephosphorylation in vitro, to ensure that any adventitious phosphorylation occurring during expression is removed. The skilled person will be aware of numerous suitable enzymes for this purpose, e.g. the λ protein phosphatase.

[0208] The activating agent may be a peptide. The peptide comprises an activation motif which is primarily responsible for mediating interaction with the catalytic domain. The activation motif may comprise a sequence derived from the native C-terminal regulatory segment of the same AGC kinase as the catalytic domain, or from the native C-terminal regulatory segment of a different AGC kinase, or may be a modified or mutated variant of either. Alternatively, the activation motif may be a synthetic sequence which does not occur naturally in an AGC kinase but which can activate the relevant catalytic domain in vitro, e.g. as described below.

[0209] The activation motif may comprise a hydrophobic motif. The hydrophobic motif is typically at least four amino acids in length, e.g. four, five or six amino acids in length, of which at least two amino acids, preferably at least three amino acids, are hydrophobic amino acids, preferably aromatic amino acids (e.g. phenylalanine, tyrosine). Preferably the hydrophobic motif comprises the sequence BXXB, where B represents an aromatic amino acid, e.g. tyrosine or phenylalanine and X is any amino acid. Thus in any sequence for an activating agent set out herein, it will be understood that phenylalanine can be replaced by tyrosine.

[0210] In a preferred embodiment, the hydrophobic motif comprises the sequence FXXF, YXXF, YXXY, FXXFX(Y/F), YXXFX(Y/F), or YXXYX(Y/F). In preferred embodiments, the hydrophobic motif comprises the sequence FXXFX(Y/F).

[0211] The activation motif preferably comprises an amino acid residue which carries a negative electrostatic charge at physiological pH. This amino acid may be located within, adjacent to or near (e.g. within one, two, three, four or five amino acids of) the hydrophobic motif, e.g. within the FXXF motif, or C-terminal of the FXXF motif, e.g. within one, two, three, four or five amino acids of the FXXF motif. The activation motif may comprise two such amino acids. In certain embodiments, one such amino acid may be located within the FXXF motif, and one may lie C terminal thereof, preferably one amino acid C-terminal thereof.

[0212] Preferably the activation motif comprises the sequence

[0213] FXXFX′, FXXFX′(F/Y), FXX′FX′, or FXX′FX′(F/Y);

[0214] YXXFX′, YXXFX′(F/Y), YXX′FX′, or YXX′FX′(F/Y);

[0215] FXXYX′, FXXYX′(F/Y), FXX′YX′, or FXX′YX′(F/Y);

[0216] YXXYX′, YXXYX′(F/Y), YXX′YX′, or YXX′YX′(F/Y);

[0217] where X′ represents an amino acid residue which carries a negative charge at physiological pH. This may be a naturally ionisable acidic amino acid, such as aspartic acid or glutamic acid. Alternatively, X′ may be charged as a result of chemical derivatisation or enzymatic modification, e.g. it may be a phosphorylated amino acid residue, such as phosphoserine or phosphothreonine. Thus, particularly when X′ is phosphoserine or phosphothreonine, X′ may carry more than one negative charge at physiological pH.

[0218] In preferred embodiments, the activation motif comprises the sequence FXXFX′, FXXFX′(F/Y), FXX′FX′, or FXX′FX′(F/Y).

[0219] In preferred embodiments the activation motif is derived from the regulatory segment of PKB or PRK2. Preferably the activation motif comprises the sequence FPQFpSY (where pS is phosphoserine), FPQFDY or FRDFDY. For example, the activating agent may comprise the whole or part of one of the sequences GLLELDQRTHFPQFpSYSASIRE, GLLELDQRTHFPQFDYSASIRE and REPRILSEEEQEMFRDFDYIADWC (PIFtide—Biondi et al., 2000).

[0220] Activation of an AGC kinase according to the present invention may be performed in vivo or in vitro.

[0221] When performed in vitro, the methods of the present invention may be used, inter alia, to generate an active conformation of an AGC kinase catalytic domain for the purposes of structural analysis. Thus the present invention further provides a method of determining a structure for an active conformation of a catalytic domain of an AGC kinase, wherein the AGC kinase in its native form is regulated by phosphorylation of a regulatory phosphorylation site residue in a C-terminal regulatory segment, said method comprising the steps of inducing the catalytic domain of the AGC kinase to adopt an active conformation by any of the methods described herein.

[0222] The method may further comprise the step of obtaining a data set for said active conformation from which a structure can be calculated, and may additionally involve the step of calculating a structure therefor.

[0223] In preferred embodiments, especially where the active conformation is to be crystallised, a stable protease-resistant form of the catalytic domain is used, preferably in recombinant form. The catalytic domain may be a PKB catalytic domain, which may lack all or substantially all of the PH domain, e.g. corresponding to residues 1 to 139, 1 to 140, 1 to 141, 1 to 142, 1 to 143, 1 to 144, or 1 to 145 of human PKBβ, or their corresponding residues in other isoforms. In a preferred embodiment, the catalytic domain lacks residues corresponding to residues 1 to 145 of human PKBβ.

[0224] Additionally or alternatively the catalytic domain may be truncated at the C-terminus, e.g. lacking amino acid residues C-terminal of position 440 in PKBβ or its equivalent. In one embodiment, the catalytic domain lacks amino acid residues C-terminal of position 460 in PKBβ or its equivalent e.g. the C-terminal 21 amino acids of PKBβ. Thus it may be a truncated derivative of PKB, e.g. truncated to positions 146-460 for PKBβ, or corresponding residues in other isoforms.

[0225] The structure may be determined by any suitable method, e.g. X-ray crystallography or NMR. Thus the method may further comprise the step of crystallising the catalytic domain of the kinase in its active conformation.

[0226] The method may include the further step of X-ray diffraction analysis of the obtained crystal.

[0227] Alternatively, the methods of the present invention may be applied in assays for assessing the ability of a candidate agent to modulating the activity of an AGC kinase.

[0228] Thus the present invention further provides a method of assessing the ability of a candidate compound to modulate the catalytic activity of an AGC kinase, which in its native form is regulated by phosphorylation of a regulatory phosphorylation site residue in a C-terminal regulatory segment, comprising the steps of

[0229] (a) providing a polypeptide comprising a catalytic domain of said kinase,

[0230] (b) forming a non-covalent complex between said polypeptide and an activating agent, wherein contact between said activating agent and said catalytic domain induces said catalytic domain to adopt an active conformation, and

[0231] (c) contacting said non-covalent complex with said candidate agent.

[0232] The method may further comprise the step of measuring the effect of the candidate agent on the AGC kinase activity.

[0233] Preferably, the AGC kinase is phosphorylated at a position corresponding to Thr-309 of human PKBβ.

[0234] The methods may be used to identify modulators, such as inhibitors or activators of AGC kinases. Suitable methods for measuring the effect of candidate compounds on AGC kinase activity will be well known to the skilled person. For example, the activity of PKB can be assayed by monitoring phosphorylation of an appropriate substrate, e.g. the peptide Crosstide, as described in the Examples.

[0235] In a further aspect, the present invention provides a non-covalent complex between a catalytic domain of an AGC kinase, which in its native form is regulated by phosphorylation of a regulatory phosphorylation site residue in a C-terminal regulatory segment, and an activating agent, wherein said catalytic domain is in an active conformation, i.e. the regions of the catalytic domain corresponding to the αB and αC helices and activation segment of PKB are in an ordered conformation.

[0236] It will be clear from the above disclosure that a catalytic domain of an AGC kinase may also be induced to adopt an active conformation if covalently linked to an activating agent such as those described above.

[0237] Thus, the present invention also provides a method of inducing a catalytic domain of an AGC kinase to adopt an active conformation, wherein the AGC kinase in its native form is regulated by phosphorylation of a regulatory phosphorylation site residue in a C-terminal regulatory segment distinct from said catalytic domain, said method comprising the steps of:

[0238] (a) providing a polypeptide comprising said catalytic domain, and

[0239] (b) covalently joining said polypeptide to an activating agent,

[0240] wherein contact between said activating agent and said catalytic domain induces said catalytic domain to adopt an active conformation.

[0241] Typically the polypeptide lacks some or all of a C-terminal regulatory domain prior to step (b). In preferred embodiments the polypeptide lacks the relevant regulatory phosphorylation site prior to step (b).

[0242] Preferably the activating agent is a peptide comprising an activation motif as described above, e.g. the peptide GLLELDQRTHFPQFDYSASIRE or REPRILSEEEQEMFRDFDYIADWC (PIFtide). Ligation of a peptide to a polypeptide may be achieved by native chemical ligation, by protein splicing, or may be catalysed by a heterologous enzyme. Methods for carrying out such ligations are reviewed in Cotton, G. J. and Muir, T. W. (1999) Chemistry and Biology 6(9): R247-R256. In some embodiments, as in all aspects of this invention, peptide mimetics, comprising non-natural amino acids, or having linkages other than peptide bonds, may advantageously be used.

[0243] In preferred embodiments a phosphopeptide derived from the C-terminal regulatory segment of an AGC kinase is ligated to the catalytic domain. Preferably, the phosphopeptide is derived from the same AGC kinase as the catalytic domain. Thus this technique enables the active phosphorylated form of the enzyme to be mimicked without needing to phosphorylate the whole enzyme. This may be particularly useful where the kinase responsible for phosphorylation in vivo has not been conclusively identified.

[0244] In a preferred embodiment a polypeptide comprising a PKB catalytic domain is ligated to a peptide comprising the whole or part of the sequence GLLELDQRTHFPQFPSYSASIRE.

[0245] In a yet further aspect, the present invention. provides a method of determining a structure for an active conformation of a catalytic domain of an AGC kinase, wherein the AGC kinase in its native form is regulated by phosphorylation of a regulatory phosphorylation site residue in a C-terminal regulatory segment distinct from said catalytic domain, said method comprising the steps of:

[0246] (a) providing a mutant AGC kinase protein comprising a catalytic domain and a C-terminal regulatory segment distinct from said catalytic domain, the protein further comprising a mutation which enhances the interaction between said regulatory segment and said catalytic domain relative to the wild type enzyme, such that an active conformation is induced in said catalytic domain, and

[0247] (b) obtaining a data set for said mutant protein from which a structure can be calculated.

[0248] The mutation enhances interaction between the regulatory segment (as described above) and the catalytic domain, such as to enable ordering of the regions of the kinase corresponding to the activation segment and αB and αC helices of PKB, without phosphorylation of a regulatory phosphorylation site in the C-terminal regulatory segment. The mutation may comprise one or more amino acid insertions, deletions or substitutions in the C-terminal regulatory segment, preferably in or around the hydrophobic motif, or in the catalytic domain, or in both C-terminal and catalytic domains. Alternatively, the mutation may involve the insertion or substitution of a number of contiguous residues of the C-terminal regulatory segment, e.g. with the corresponding residues from a second AGC kinase. Such a mutant AGC kinase may be considered to be a chimeric kinase.

[0249] Preferably, the C-terminal regulatory segment is mutated so that its interaction with the wild-type catalytic domain is enhanced. Preferably the mutation is made in or around the hydrohobic motif of the C-terminal regulatory segment, i.e. the region corresponding to the sequence FPQFSY of PKBβ (amino acid residues 470-475). The mutation may comprise substitution, deletion or insertion of one or more amino acids, e.g. 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, or 20 amino acids. In preferred embodiments the regulatory phosphorylation site is mutated.

[0250] In preferred embodiments, the mutation comprises the introduction into the C-terminal regulatory segment of a residue which carries an electrostatic charge at physiological pH, preferably a negative electrostatic charge, e.g. aspartic acid or glutamic acid.

[0251] In a preferred embodiment the amino acid residue which would be phosphorylated to activate the wild-type enzyme (e.g. the residue corresponding to Ser-474 of PKBβ) is mutated to a residue which carries a negative electrostatic charge at physiological pH, e.g. aspartic acid or glutamic acid. For example, where the AGC kinase is PKBβ, the mutation may involve alteration of the sequence FPQFSY to FPQFDY.

[0252] In other embodiments, the mutation may involve the substitution of a number of contiguous residues of the C-terminal regulatory segment, e.g. with the corresponding residues from a second AGC kinase. Thus the sequence FPQFSY of PKBβ may be replaced by the sequence FRDFDY from PRK2. The chimera may contain further sequences from the second kinase, e.g. one or more of the flanking residues in the sequence GLLELDQRTHFPQFDYSASIRE from PKBβ may be replaced by one or more corresponding residues of the sequence REPRILSEEEQEMFRDFDYIADWC from PRK2 (PIFtide).

[0253] Additionally or alternatively, the catalytic domain may be mutated to enhance its interaction with the wild-type C-terminal regulatory segment, or with a mutated C-terminal regulatory segment. Thus the catalytic domain may be mutated in or around the binding groove which interacts with the C terminal regulatory segment. For example, polar or charged residues (e.g. serine, threonine, aspartic acid, glutamic acid, lysine, etc.) may be mutated to more hydrophobic residues (e.g. phenylalanine, tyrosine, etc.), or hydrophobic residues replaced by more hydrophobic or larger hydrophobic residues, in order to enhance the interaction between the catalytic domain and the hydrophobic motif of the regulatory segment.

[0254] Possible target residues include V194 and V198 of PKBβ. These may, for example, be replaced by the corresponding residues of the hydrophobic groove from PKA. This is capable of binding the regulatory segment of PKA without phosphorylation, which implies that the hydrophobic interactions involved are stronger than are seen in PKB. Thus possible substitutions include V194I and V198L.

[0255] Additionally or alternatively, substitutions may be made which enhance the binding of the catalytic domain to a negative charge of the regulatory segment, e.g. incorporating further positive charges. A possible target residue is S201; therefore a possible substitution is S201K.

[0256] Alternatively, both catalytic domain and C-terminal regulatory segment may be mutated in order to enhance the affinity between them. Mutants may be prepared for example, by site-specific mutagenesis, or incorporation of natural or unnatural amino acids.

[0257] In preferred embodiments, especially where the mutant AGC kinase is to be crystallised, a stable protease-resistant form of the catalytic domain truncated at the N-terminus is used. The kinase may lack some or all of the wild-type residues upstream of the catalytic domain, e.g. corresponding to all or substantially all of the PH domain of PKB, e.g. corresponding to residues 1 to 139, 1 to 140, 1 to 141, 1 to 142, 1 to 143, 1 to 144, 1 to 145, 1 to 146, 1 to 147, 1 to 148, 1 to 149 or 1 to 150 of human PKBβ, or their corresponding residues in other isoforms. In a preferred embodiment the kinase lacks residues corresponding to residues 1 to 145 of PKBβ.

[0258] In a further aspect, the present invention provides a mutant AGC kinase protein, wherein the AGC kinase in its native form is regulated by phosphorylation of a regulatory phosphorylation site residue in a C-terminal regulatory segment, said mutant AGC kinase protein comprising a catalytic domain and a C-terminal regulatory segment distinct from said catalytic domain, and having an N-terminus corresponding to residue 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149 or 150 of PKBβ, or their corresponding residues in other isoforms, the mutant AGC kinase protein comprising a mutation which enhances the interaction between said regulatory segment and said catalytic domain relative to the wild type enzyme, such that an active conformation is induced in said catalytic domain.

[0259] The mutation enhances interaction between the regulatory segment and the catalytic domain, such as to enable ordering of the regions of the kinase corresponding to the activation segment and αB and αC helices of PKB, without phosphorylation of the regulatory segment, and may have any of the characteristics described above.

[0260] In a preferred embodiment the kinase has an N-terminus corresponding to residue 146 of PKBβ.

[0261] In a further aspect, the present invention provides nucleic acids encoding the mutant ACC kinase polypeptides as described herein.

[0262] Throughout this specification, where nucleic acids are referred to, they may be wholly or partially synthetic. In particular they may be recombinant in that nucleic acid sequences which are not found together in nature (do not run contiguously) have been ligated or otherwise combined artificially. Alternatively they may have been synthesised directly e.g. using an automated synthesiser.

[0263] Nucleic acid according to the present invention may be polynucleotides or oligonucleotides, and may include cDNA, RNA, genomic DNA (gDNA) and modified nucleic acids or nucleic acid analogs.

[0264] Where a nucleic acid (or nucleotide sequence) of the invention is referred to herein, the complement of that nucleic acid (or nucleotide sequence) will also be embraced by the invention. The ‘complement’ in each case is the same length as the reference, but is 100% complementary thereto whereby by each nucleotide is base paired to its counterpart i.e. G to C, and A to T or U.

[0265] The nucleic acids of the present invention may differ from any specific sequences recited or referred to herein by a change which is one or more of addition, insertion, deletion and substitution of one or more nucleotides of the sequences shown, e.g. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 40, 50 or more nucleotides. Preferably the reading frame is maintained. Changes to a nucleotide sequence may result in an amino acid change at the protein level, or not, as determined by the degeneracy of the genetic code.

[0266] Nucleic acids of the present invention may be provided as part of a vector, and also provided by the present invention is a vector comprising nucleic acid as described herein, particularly vectors from which the polypeptide can be expressed under appropriate conditions, and a host cell containing any such vector or nucleic acid.

[0267] ‘Vector’ is defined to include, inter alia, any virus, plasmid, cosmid, or phage vector in double or single stranded linear or circular form which may or may not be self transmissible or mobilizable, and which can transform a prokaryotic or eukaryotic host either by integration into the cellular genome or exist extrachromosomally (e.g. autonomous replicating plasmid with an origin of replication).

[0268] Generally speaking, those skilled in the art are well able to construct vectors and design protocols for recombinant gene expression. Suitable vectors can be chosen or constructed, containing appropriate regulatory sequences, including promoter sequences, terminator fragments, polyadenylation sequences, enhancer sequences, marker genes and other sequences as appropriate. For further details see, for example, Molecular Cloning: a Laboratory Manual: 2nd edition, Sambrook et al, 1989, Cold Spring Harbor Laboratory Press or Current Protocols in Molecular Biology, Second Edition, Ausubel et al. eds., John Wiley & Sons, 1992.

[0269] Specifically included are shuttle vectors by which is meant a DNA vehicle capable, naturally or by design, of replication in two different host organisms, which may be selected from actinomycetes and related species, bacteria and eukaryotic (e.g. higher plant, mammalian, insect, yeast or fungal cells).

[0270] A vector including nucleic acid according to the present invention need not include a promoter or other regulatory sequence, particularly if the vector is to be used to introduce the nucleic acid into cells for recombination into the genome.

[0271] Preferably a nucleic acid sequence of the present invention in the vector is under the control of, and operably linked to, an appropriate promoter or other regulatory elements for transcription in a host cell such as a microbial, e.g. bacterial, or yeast cell, or an insect or mammalian cell. The vector may be a bifunctional expression vector which functions in multiple hosts. In the case of genomic DNA, this may contain its own promoter or other regulatory elements and in the case of cDNA this may be under the control of an appropriate promoter or other regulatory elements for expression in the host cell

[0272] By “promoter” is meant a sequence of nucleotides from which transcription may be initiated of DNA operably linked downstream (i.e. in the 3′ direction on the sense strand of double-stranded DNA).

[0273] “Operably linked” means joined as part of the same nucleic acid molecule, suitably positioned and oriented for transcription to be initiated from the promoter. DNA operably linked to a promoter is “under transcriptional initiation regulation” of the promoter.

[0274] In a preferred embodiment, the promoter is an inducible promoter. The term “inducible” as applied to a promoter is well understood by those skilled in the art. In essence, expression under the control of an inducible promoter is “switched on” or increased in response to an applied stimulus. The nature of the stimulus varies between promoters. Some inducible promoters cause little or undetectable levels of expression (or no expression) in the absence of the appropriate stimulus. Other inducible promoters cause detectable constitutive expression in the absence of the stimulus. Whatever the level of expression is in the absence of the stimulus, expression from any inducible promoter is increased in the presence of the correct stimulus.

[0275] Thus these aspects of the invention provide a gene construct, preferably a replicable vector, comprising a promoter (optionally inducible) operably linked to a nucleotide sequence provided by the present invention.

[0276] Preferably the vector is capable of providing expression in an insect cell, such as an Sf9 cell, especially where the expressed product is to be crystallised. The polypeptide may be encoded by a vector construct substantially similar to those disclosed herein.

[0277] The present invention also encompasses method of making peptides or polypeptides as disclosed, the method including the step of expressing said polypeptide or peptide from nucleic acid encoding it, which in most embodiments will be nucleic acid according to the present invention. This may conveniently be achieved by growing a host cell containing such a vector in culture under appropriate conditions which cause or allow expression of the polypeptide. Polypeptides and peptides may also be expressed in in vitro systems, such as reticulocyte lysates, as will be appreciated by the skilled person.

[0278] Systems for cloning and expression of a polypeptide in a variety of different host cells are well known. Suitable host cells include bacteria, eukaryotic cells such as mammalian and yeast, and baculovirus-based insect expression systems. Mammalian cell lines available in the art for expression of a heterologous polypeptide include Chinese hamster ovary cells, HeLa cells, baby hamster kidney cells, COS cells and many others.

[0279] Although certain specific amino acid sequences are referred to herein, e.g. in the context of peptides capable of activating AGC kinases, it will be appreciated that similar sequences having functionally insignificant changes are equally appropriate for practising the present invention. Therefore amino acids present in the said sequences can be replaced by other amino acids having similar properties, for example hydrophobicity, hydrophobic moment, antigenicity, propensity to form or break a-helical or β-sheet structures, and so. Substitutional variants of a protein are those in which at least one amino acid in the protein sequence has been removed and a different residue inserted in its place. Amino acid substitutions are typically of single residues but may be clustered depending on functional constraints e.g. at a crystal contact. Preferably amino acid substitutions will comprise conservative amino acid substitutions. Insertional amino acid variants are those in which one or more amino acids are introduced. This can be amino-terminal and/or carboxy-terminal fusion as well as intrasequence. Examples of amino-terminal and/or carboxy-terminal fusions are affinity tags, maltose binding protein (MBP) tags, and epitope tags.

[0280] Amino acid substitutions, deletions and additions which do not significantly interfere with three-dimensional structure will depend, in part, on the region of the molecule where the substitution, addition or deletion occurs. In highly variable regions of the molecule, non-conservative substitutions as well as conservative substitutions may be tolerated without significantly disrupting the three-dimensional structure of the molecule. In highly conserved regions, or regions containing significant secondary structure, conservative amino acid substitutions are preferred.

[0281] Conservative amino acid substitutions are well-known in the art, and include substitutions made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity and/or the amphipathic nature of the amino acid residues involved. For example, negatively charged amino acids include aspartic acid and glutamic acid; positively charged amino acids include lysine and arginine; amino acids with uncharged polar head groups having similar hydrophilicity values include the following: leucine, isoleucine, valine; glycine, alanine; asparagine, glutamine; serine, threonine; phenylalanine, tyrosine. Other conservative amino acid substitutions are well known in the art.

[0282] In some instances, it may be particularly advantageous or convenient to substitute, delete and/or add amino acid residues to a particular binding site or catalytic residue, in order to provide convenient cloning sites in cDNA encoding the polypeptide, to aid in purification of the polypeptide, etc. Such substitutions, deletions and/or additions which do not substantially alter the three dimensional structure of the wild-type kinase will be apparent to those having skills in the art.

[0283] Particular embodiments of the invention will now be described, by way of example only, with reference to the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

[0284]FIG. 1 shows a comparison of PKB and PKA structures, with ribbon representations of PKA (A) and PKB (B). PKA and PKB were superimposed onto their C-terminal lobes. Phe 294 of the DFG motif of PKB occupies a site equivalent to the adenine pocket of the nucleotide binding site of PKA. (C) Stereo view of a superimposition of PKA and PKB to show different relative orientations of their N- and C-terminal lobes. Conformational differences in C-lobe are localised to the activation segment and αF/αG loop Figure drawn using BOBSCRIPT (Esnouf, 1997) and RASTER3D (Merit and Murphy, 1994)

[0285]FIG. 2 shows the structure of the N-terminal Lobe:

[0286] (A) Flexibility of αB- and αC-helices. 2Fo-Fc electron density map contoured at 1σ of a portion of the N-terminal lobe of pΔPH-PKB-ΔC (β3, β4, β5-strands, βB- and βC-helices). Electron density for the β-sheet is well resolved, whereas the αB- and αC-helices are disordered. The main-chain of the N-terminal lobe and hydrophobic motif of PKA is shown superimposed onto PKB.

[0287] (B and C) Role of hydrophobic motif to order the αB- and αC-helices and link to activation segment. (B) Interactions of hydrophobic motif of PKA with the β3, β, β5-strands and αB- and αC-helices of the N-terminal lobe. Phe 347 and Phe 350 are buried by hydrophobic residues. Glu 349 and C-terminal carboxylate form hydrogen bonds with basic residues of the αC-helix. (C) Disorder of the αB- and αC-helices of PKB is correlated with absence of bound hydrophobic motif. In (B) bracketed residues corresponds to PKB numbering.

[0288]FIG. 3. Role of αC-helix to regulate conformation of PKA and PKB and structure of activation segment and DFG motif. (A) αC-helix stabilises an active state of PKA by interaction with pThr 197 of the activation segment via His 87, and Phe 185 of the DFG motif via Ile 93 and Leu 94. (B) In PKB, disorder of the αC-helix prevents His 196 from interacting with pThr 309. Loss of interactions with Phe 294 of the DFG motif binds within the nucleotide-binding site of ATP.

[0289]FIG. 4 shows a multiple sequence alignment of the catalytic domains and C-terminal regulatory segments of various AGC-family protein kinases. Invariant residues are shown with dark shading and conserved residues with light shading. The position of critical functional residues are indicated with a dark arrow and numbered according to PKA residues. PKB Thr 309 and Ser 474 phosphorylation sites are indicated. The conserved AGC-kinase hydrophobic motif is shown and mutated residues of PKB that influence PIFtide activation (FIG. 7B) are indicated by light arrows. Figure drawn using ALSCRIPT (Barton, 1993).

[0290]FIG. 5 illustrates the activation of PKB by hydrophobic motif peptides and complex formation between PKB and PIFtide.

[0291] (A) Dose response curve for the activation of ΔPH-PKB-ΔC by various synthetic 23 residue peptides derived from the PKB regulatory segment. : PKB HM-P has a phosphoserine residue at position 474; ▾: PKB HM-D has aspartate at position 474; o: has an unphosphorylated serine residue at position 474 and so corresponds to the wild type sequence.

[0292] (B) Dose response curve for the activation of (p)ΔPH-PKB-ΔC by PIFtide a synthetic 24 residue peptide encompassing the PRK2 HM motif. : PIFtide and pΔPH-PKB-ΔC, ▾: PIFtide and ΔPH-PKB-ΔC, ∘: mutant PIFtide(D>A) and pΔPH-PKB-ΔC. PIFtide can bind to ΔPH-PKB-ΔC but cannot activate it in the absence of Thr-309 phosphorylation.

[0293] (C) Isothermal titration calorimetry measurements of the binding of PIFtide to pΔPH-PKB-ΔC (left) and ΔPH-PKB-ΔC (right). Upper panel, raw data of the titration of PIFtide into pΔPH-PKB-ΔC. Lower panel, integrated heats of injections, corrected for the heat of dilution, with the solid line corresponding to the best fit of the data using the MicroCal software.

[0294]FIG. 6 shows that conserved residues of the hydrophobic motif, and residues of the N-lobe of PKB, are required for PIFtide and PKB HM-peptide mediated stimulation of PKB kinase activity. Mutations of conserved hydrophobic motif residues of PIFtide and PKB HM-peptide reduce or eliminate their potential to activate ΔPH-PKB-ΔC phosphorylated on Thr 309.

[0295] Mutations of hydrophobic and electrostatic residues of the ΔPH-PKB-ΔC N-lobe hydrophobic groove reduces the stimulation of PKB activity by 130 pM PIFtide. The position of mutated residues on PKA and PKB (R202D, V194A-V198A and L225A) are shown in FIG. 4.

[0296]FIG. 7 is a comparison of the amino acid sequences of human PKBα, PKBβ and PKBγ. The PH and catalytic domains are shown boxed, and are connected by the linker domain. The GXXGXG ATP binding site, the catalytic lysine residue, and the regulatory phosphorylation sites are shown in bold type.

[0297]FIG. 8 shows ribbon diagrams of the structures obtained for PKB-PIF and PKB S474D, illustrating the positions of the AMP-PNP moiety and the GSK-3 substrate peptide.

DETAILED DESCRIPTION OF THE INVENTION

[0298] Inactive Structures of PKB

[0299] Limited trypsinolysis of full length PKBβ purified from Sf9 cells led the present inventors to the identification of a protease resistant domain with an N-terminus at Lys-146, referred to as ΔPH-PKB. Lys-146 is located within the structurally diverse region linking the pleckstrin homology (PH) and kinase domains of PKB, close to the N-terminus of the corresponding β1-strand of PKA.

[0300] During the course of the purification, partial cleavage of a C-terminal 3 kDa fragment was observed, suggesting conformational flexibility at the C-terminus of the protein. Human PKBα, PKBβ and PKBγ sequences are structurally diverse within a 12 residue region C-terminal to the conserved PP(D/E) motif (residues 452-454 of PKBβ), preceding the C-terminal hydrophobic motif, and corresponding to the C-terminus of the PKBβ splice variant.

[0301] Using this information, the present inventors constructed a number of new PKB baculovirus Fastbac entry vectors for the generation of PKB insect cell/baculovirus expression systems, and expressed the β and γ-isoforms of PKB as the kinase domain, with an N-terminus at Lys-146 (i.e. lacking the PH domain), with and without the C-terminal 21 residues that includes the hydrophobic regulatory segment. These two kinase domains are termed ΔPH-PKB and ΔPH-PKB-ΔC, respectively.

[0302] These expression systems express high levels of protein, which have been purified to homogeneity. Moreover, PDK1has been expressed using the insect cell/baculovirus system and MAPKAPK2 in the E. coli expression system to enable phosphorylation of PKBβ on Thr309 and Ser474, respectively.

[0303] To prepare defined phosphorylated states of PKB, phosphorylation and dephosphorylation reactions were performed using PDK1 (for pThr-309) and the non-specific λ-protein phosphatase, respectively.

[0304] Distinct phosphorylated states of the protein were resolved using hydrophobic interaction chromatography.

[0305] The phosphorylation state of the protein was analysed by Western blots using phospho-specific antibodies, and the stoichiometry and sites of phosphorylation were quantitatively assessed by mass spectroscopic analysis of trypsin-generated peptides of the protein.

[0306] Crystals were successfully obtained for the PKBβ derivatives, and structures determined for ΔPH-PKBβ-ΔC, pΔPH-PKBβ-ΔC and ΔPH-PKBβ by X-ray crystallographic techniques. High resolution structures were obtained, apparently showing the catalytic domain of PKBβ in the inactive conformation.

[0307] The phosphorylation state of the protein was analysed by Western blots using phospho-specific antibodies, and the stoichiometry and sites of phosphorylation were quantitatively assessed by mass spectroscopic analysis of trypsin-generated peptides of the protein. The three crystal forms of human PKBβ are; (i) pΔPH-PKB-ΔC, phosphorylated in vitro on Thr-309, (ii) ΔPH-PKBβ-ΔC, not phosphorylated on Thr-309, and (iii) ΔPH-PKBβ, dephosphorylated in vitro.

[0308] Two different batches of crystals, having different resolution, were produced for crystal form (i), i.e. pΔPH-PKB-ΔC.

[0309] Results

[0310] Each of the crystals belonged to the tetragonal space group P4₁2₁2, and accommodated one molecule of PKB per asymmetric unit with cell parameters as follows:

[0311] pΔPH-PKB-ΔC (first batch): a=149.33 Å, b 149.33 Å, c=39.77 Å; pΔPH-PKB-ΔC (second batch): a 148.40 Å, b 148.40 Å, c 38.55 Å;

[0312] ΔPH-PKB-ΔC: a 149.70 Å, b=149.70 Å, c=39.19 Å;

[0313] ΔPH-PKB: a =149.52 Å, b=149.52 Å, c=39.06.

[0314] Resolution was determined to be 2.8 Å for the first batch and 2.3 Å for the second batch of PΔPH-PKB-ΔC crystals, 2.7 Å for ΔPH-PKB-ΔC and 2.5 Å for ΔPH-PKB.

[0315] The current refined R-factor:

[0316] (Σ|F₀-F_(c)|/Σ|F₀|, where F₀=observed amplitude, and F_(c)=calculated amplitude) is as follows:

[0317] pΔPH-PKBβ-ΔC (second batch): 0.237 to 2.3 Å resolution.

[0318] ΔPH-PKBβ-ΔC: 0.238 to 2.7 Å resolution.

[0319] ΔPH-PKBβ: 0.254 to 2.5 Å resolution.

[0320] More detailed information about the data collection and refinement statistics are provided for all crystals except the first batch of pΔPH-PKB-ΔC is provided in Table 1 below. TABLE 1 Crystallographic Data Collection and Refinement Statistics for Inactive Crystals Protein pΔPH-PKBβ-ΔC ΔPH-PKBβ-ΔC ΔPH-PKBβ Amino acid residues 146-460 146-460 146-481 Phosphorylation Thr-309 — — Space group (Z) P4₁212 (1) P4₁212 (1) P4₁212 (1) Cell parameters a 148.40 149.70 149.52 (Å) c (Å) 38.55 39.19 39.06 X-ray source ID14eh4 ESRF ID14eh4 ESRF ID14eh4 ESRF Resolution (Å) 2.3 2.7 2.5 Observations (N) 113 677 50 875 92 809 Unique (N) 18 905 12 147 16 090 Completeness (%) 96.1 94.2 99.7 ^(a)R_(sym) 0.050 (0.243) 0.065 (0.236) 0.057 (0.255) I/σI 21.0 18.0 14.8 Refinement Resolution range 35-2.3 35-2.75 35-2.6 (Å) Reflections used (N) 17 576 10 320 14 317 R_(free) set (N) (%) 1398 (7.1) 1199 (9.9) 1598 (10.0) ^(b)R_(cryst)/R_(free) 0.237/0.309 0.238/0.30 0.254/0.314 Protein atoms (N) 2 198 2 198 2198 Solvent atoms (N) 154 27 125 r.m.s.d. bond angles 1.54 1.57 1.53 (°) r.m.s.d. bond 0.0105 0.0112 0.0104 lengths (Å)

[0321] Values in parentheses are for the highest shell ^(a)R_(sym)=Σ_(h)Σ_(j)|<−I(h)_(j)|/Σ_(h)Σ_(j)<I(h)>, where <I(h)> is the mean intensity of symmetry-equivalent reflections. ^(b)R_(cryst/free)=Σ∥F_(obs)|−|F_(calc)∥/Σ|F_(obs)|, where F_(obs) and F_(calc) are the observed and calculated structure factors, respectively. Root-mean-square deviations relate to the Engh and Huber parameters.

[0322] Overall Description of the Inactive Structure and Comparison with PKA

[0323] The structure of pΔPH-PKB-ΔC is essentially identical to those of ΔPH-PKB-ΔC and ΔPH-PKB (rms deviations of 0.3 Å and 0.4 Å, respectively), and this similarity to inactive forms of PKB, together with features of the structure, indicates that the crystallisation conditions favoured the inactive conformation of pΔPH-PKB-ΔC. Because of the higher resolution of the pΔPH-PKB-ΔC crystal structure, most of the discussion is focussed on this form.

[0324] The structure of pΔPH-PKBβ-ΔC (residues 146-460) resembles the catalytic domain of other protein kinases (reviewed by Johnson et al., 1996). In particular, it resembles that of the catalytic subunit of PKA (FIG. 1). The PKB molecule is organised into an N-terminal and C-terminal lobe, with the N-terminal lobe (residues 146-233) formed from a 5-membered P-sheet and flanking a-helix, αA (equivalent to αC of PKA). The C-terminal lobe (residues 234-450) is predominantly a-helical and is joined to the N-terminal lobe via a single polypeptide chain connection.

[0325] The catalytic site of PKB is situated at the interface of the N and C-terminal lobes and is formed from residues of the catalytic loop (residues 274-282), and the activation segment (residues 304-312) of the C-terminal lobe, together with the ATP binding site and the αA helix of the N-terminal lobe. The ATP binding site consists of a hydrophobic pocket formed by residues (Val158, Val166) that interact with the adenine ring of the nucleotide, and a more hydrophilic region that interacts with the ribose ring and phosphate groups. By analogy with other protein kinases (Hubbard, 1997), the activation segment provides the binding site for the peptide substrate, orientating the substrate amino acid towards the phosphates of the ATP.

[0326] The catalytic mechanism of all protein kinases is similar and involves a phosphoryl transfer reaction from the γ-phosphate group of the ATP onto the hydroxyl group of the substrate amino acid residue. The reaction commences with the nucleophilic attack by the hydroxyl group of the substrate amino acid residues onto the γ-phosphate of ATP. A catalytic base in PKBp, Asp265, facilitates this attack by increasing the nucleophilicity of the substrate hydroxyl group. The phosphate moieties of ATP are coordinated by the glycine rich loop and Lys1181 of the N-terminal lobe and by a Mg²⁺ ion that interacts with Asp293 of the protein kinase C-terminal lobe.

[0327] PKA and PKB share essentially the same secondary structure topology, except that in PKB there is no counterpart to the αA-helix of PKA, and some of the structural elements of PKB are disordered. The architecture of PKA consists of an N-terminal lobe based on a 5-stranded β-sheet, with two α-helices (the αB- and αC-helices), and a larger, mainly a-helical C-terminal lobe, containing the activation segment. The catalytic site for ATP is located at the interface of the two lobes, whereas the substrate peptide-binding site is within the C-lobe, centred on the activation segment.

[0328] The inactive state of PKB differs in structure from the catalytically active form of PKA in a number of respects that are important for the regulation of PKB by multi-site phosphorylation. These differences involve the overall juxtaposition of the N- and C-lobes of the kinase, and structural disorder of the αB- and αC-helices of the N-lobe, activation segment of the C-lobe, and C-terminal regulatory segment. When superimposed, equivalent Cα-atoms of PKB and the ternary complex of PKA differ by an rms deviation of 2.3 Å (FIG. 1C). This deviation is larger than the expected value of 1.2 Å for a pair of proteins with 43% sequence identity (Cothia and Lesk, 1986), and results from differences in the relative orientations of the N- and C-terminal lobes of PKA and PKB When superimposed individually, differences in conformation between the equivalent N- and C-lobes of PKA and PKB are seen to be localised to the β1-strand and αC-helix in the N-lobe, and DFG motif and αF/αG loop in the C-lobe.

[0329] PKA adopts open and closed conformational states resulting from relative rotations of the N- and C-lobes that are associated with various substrate-PKA complexes, with the ternary-PKA complex adopting a closed state, and the apo and binary complexes being more open. However, the relative position of the N- and C-lobes of PKB, do not resemble any of the various PKA-ligand complexes. Compared with the PKA-ternary complex, the N-lobe of PKB is rotated by 20° relative to its C-lobe, causing catalytic site residues from the two lobes to be misaligned.

[0330] Comparison of a number of activated protein kinase structures indicates that their N- and C-terminal lobes adopt similar relative configurations. For example, the Cα-Cα distance of two residues (Val-57 and Leu-173) that span the nucleotide-binding site in the PKA ternary complex is 12.9 Å, the same as that between equivalent residues of the phosphorylated insulin receptor kinase (Hubbard, 1997). In contrast, for PKB this distance is 15.2 Å.

[0331] Structural Disorder in PKB

[0332] In addition to variations in their overall bilobal configuration, the structures of PKB and PKA differ in other respects that are significant for the reduced catalytic activity of unphosphorylated and mono-phosphorylated forms of PKB. In the inactive PKB structures, three inter-related regions of the polypeptide chain are disordered; (i) the αB- and αC-helices of the N-terminal lobe, (ii) the activation segment between the invariant DFG and APE motifs, and (iii) the C-terminal regulatory segment in ΔPH-PKB. Concerted disorder to order transitions of these regions, linked to a conformational change of the activation segment DFG motif, and reorganisation of the N- and C-lobes, are required to generate a catalytically active protein kinase on phosphorylation of Thr-309 and Ser-474.

[0333] Although the structures of the three disordered regions are inter-dependent, each region is described in turn, before discussing the biological implications that these regions are disordered. This analysis is greatly assisted by the ability to compare the structural differences between an inactive PKB molecule with that of the related active PKA catalytic subunit, the latter serving as a model for an active phosphorylated form of PKB.

[0334] Flexibility of the αB- and αc-helices

[0335] Within the N-terminal lobe of PKB, the β-sheet is well ordered, however, residues Ala-189 to Thr-207, equivalent to the αB-helix and the majority of the αC-helix of PKA, are highly mobile, as judged by disorder in the weighted 2Fo-Fc electron density, and composite simulated annealing omit maps, and analysis of the atomic temperature-factors (FIG. 2A). Specifically, for all crystal forms, there is no visible electron density to account for residues Ala-189 to Thr-197, whose counterparts in PKA form the C-terminus and N-terminus of the αB- and αC-helices, respectively.

[0336] Electron density corresponding to the main-chain of the remaining residues of the αC-helix is fragmented, and the side-chains of these residues are disordered. The short αB-helix, which connects the αC-helix with the central β3-strand of the P-sheet, is unique to the AGC-protein kinases, and causes the N-terminus of the αC-helix to be displaced from the β4/β5-strands of the P-sheet (FIG. 1, 2). As a consequence, the αC-helix packs less tightly against the hydrophobic side-chains of the β-sheet, compared with other protein kinases, and, significantly a deep surface groove is created at the interface between the αB/αC-helices and P-sheet. In PKA this groove permits interactions between the N-terminal lobe and C-terminal hydrophobic motif.

[0337] The importance of the conserved αC-helix for both catalytic and regulatory functions has been demonstrated for many protein kinases. An invariant glutamate residue located near the N-terminus of the helix, (Glu-91 of PKA, Glu-200 of PKB), is responsible for its catalytic function by forming a hydrogen bond with an invariant lysine side-chain; Lys-72 of PKA (FIG. 3). Lys-72 in turn coordinates the P-phosphate of ATP in active protein kinases.

[0338] In addition, because the αC-helix is responsible for the major interfacial contacts between the N- and C-lobes, particularly via its interactions with the DFG motif of the activation segment, it plays a role both in aligning catalytic and substrate-peptide binding residues of the C-terminal lobe, and in governing the overall juxtaposition of the N- and C-lobes.

[0339] Motion of the αC-helix represents a general mechanism for the modulation of kinase catalytic activity, and the integration of diverse regulatory signals. For example, the position of the αC-helix of CDK2 is shifted to an active conformation on the association of the monomeric CDK2 subunit with cyclin A (Jeffrey et al., 1995), and similar changes in the αC-helix are observed on activation of the insulin receptor kinase and ERK2 on phosphorylation of their activation segments (Hubbard 1997; Canagarajah et al., 1997), and in the Src- and Eph-family tyrosine kinases (Sicheri et al., 1997, Xu et al., 1997; Wybenga-Groot et al., 2001). Significantly, in many protein kinases that are regulated by phosphorylation of the activation segment, the αC-helix provides a basic residue to contact the phosphate group of the phospho-amino acid, hence coordinating the relative positions of the αC-helix with the activation segment, and the N- and C-terminal lobes. In PKA, the basic residue is His-87 at the N-terminus of the αC-helix, which contacts pThr-197 of the activation segment (FIG. 2, 3). In the inactive state of PKB, His-196 and Glu-200 of the αC-helix (equivalent to His-87 and Glu-91 of PKA) are disordered, and contacts between Glu-200 and Lys-181 (Lys-72 of PKA), and those between His-196 and pThr-309, are not formed (FIG. 3).

[0340] Disorder of the αC-helix contributes to an inactive state of PKB for two reasons. First, the side-chain of Lys-181 is not properly positioned, and second, there are associated changes in the structure of the activation segment, and relative disposition of the N- and C-terminal lobes. As described below, disorder of the αB- and αC-helices of PKB is coupled to the disorder of its non-phosphorylated C-terminal regulatory segment.

[0341] Role of the C-terminal Regulatory Segment

[0342] A distinctive structural feature of PKA, not usually observed in other protein kinases, is the interaction of the extreme C-terminus of the protein with its N-terminal lobe. In PKA, the polypeptide chain emerges from the C-terminal lobe and extends along the entire length of the bi-lobal structure. At the tip of the N-lobe, the chain forms a reverse turn, allowing the extreme C-terminal eight residues of PKA to lie within an amphipathic/hydrophobic groove on the surface of the N-lobe (FIGS. 1A, 2B). Importantly, these interactions are mediated by residues of the C-terminal hydrophobic motif, which contact the surface groove formed by residues of the αB- and αC-helices, and the 5-strand of the N-lobe. The dominant interactions at the interface involve those between the side chains of the two phenylalanine residues of the hydrophobic motif, Phe-347 and Phe-350, which protrude into a pocket formed by hydrophobic residues of the N-lobe (FIG. 2). Specifically, the phenyl-ring of Phe-347 is extensively buried by the side-chains of five amino acids: Lys-76, Val-79 and Val-80 of the αB-helix, Ile-85 of the αC-helix, and Leu-116 of the P5-strand, whereas the side-chain of Phe-350 contacts Leu-89 and Lys-92 of the αC-helix, and Leu-116 and Met-118 of the β5-strand (FIG. 2B). At one end of the channel, two adjacent basic residues of the αC-helix form salt-bridge interactions with two carboxylate groups of the hydrophobic motif.

[0343] In all three inactive crystal structures of PKB, residues corresponding to the regions of the αB- and αC-helices of PKA that interact with the hydrophobic motif, are disordered, and this probably results from loss of interactions with the hydrophobic motif of PKB (FIG. 2A, C). In the crystal structures of ΔPH-PKB-ΔC, the 21 residues C-terminal to Ser-460 were removed from the expression construct, and therefore potential interactions between the hydrophobic motif and the N-lobe are not possible. Moreover, in these structures, electron density for residues C-terminal to Asp-441 is not visible, suggesting that they are conformational disordered. However, in the ΔPH-PKB structure, which contains a non-phosphorylated hydrophobic motif, and therefore retains the potential to interact with the N-lobe, we are also unable to detect visible electron density for residues C-terminal to Asp-441, indicating that the C-terminal 40 residues, including the hydrophobic motif, are mobile.

[0344] Conformation of the Activation Segment and Nucleotide Binding Site

[0345] The activation segment is central to the regulation and catalytic activity of protein kinases (Johnson et al., 1996). In the structure of active protein kinases, the activation segment contributes to the correct conformation of the catalytic site and ATP-binding residues, and participates in peptide-substrate recognition and specificity. By functioning as a link between the N- and C-lobes, conformational changes of the activation segment, resulting from regulatory phosphorylation, and/or modulator subunits, are coupled to global changes in kinase structure. In all three crystal forms of PKB, a contiguous region of the activation segment (residues 297 to 312) located between the invariant DFG and APE motifs, and including (p)Thr-309, is disordered. There is no electron density visible for these residues in either the 2Fo-Fc, or the simulated annealling omit maps. It was determined that pΔPH-PKB-ΔC was phosphorylated on Thr-309 by quantitative mass spectroscopic analysis of a tryptic digest of the protein. Moreover, it was confirmed that the protein forming the pΔPH-PKB-ΔC crystal was phosphorylated by Western blot analysis of a dissolved crystal using pThr-309-specific antibodies.

[0346] In the inactive PKB structures, residues of the DFG sequence are ordered, but adopt a different conformation from their counterparts in PKA, functioning to inhibit PKB by disrupting the nucleotide-binding site (FIG. 3). The DFG motif of activated protein kinases is important because its Asp residue (Asp-184 of PKA) coordinates the Mg²⁺ ion responsible for contacting the β- and γ-phosphates of ATP. In PKB, the side-chain of Asp-293 (equivalent to Asp-184 of PKA) is directed away from the ATP binding site (FIG. 3B). This structural change is accompanied by a shift in the positions of Phe-294 and Gly-295 of the DFG motif, and main-chain of Leu-296, towards the glycine-rich β1-β2 nucleotide-binding loop of the N-lobe. Motion of the DFG-motif residues is accommodated by a change in the relative orientation of the N- and C-lobes of PKB, compared with PKA, to avoid their clash with the β1-strand of the N-lobe. Relative to the conformation of the equivalent Phe-185 residue of PKA, the phenyl ring of Phe-294 is displaced by as much as 10 Å, and is situated within the hydrophobic adenine-binding pocket for ATP. This structural feature of PKB is similar to the inactive state of IRK where the Phe residue of the DFG motif blocks the nucleotide-binding site by mimicking the ATP adenine ring (Hubbard et al., 1994). Thus, in PKB, the ATP binding site is disrupted both because the Lys-181 and Asp-293, residues responsible for coordinating the phosphate groups, are displaced, and because ATP is sterically hindered from binding by Phe-294. In PKA, and in the structures of other activated protein kinases, Phe-185 of the DFG motif packs deep into the interface between the two lobes, and forms intimate contacts with hydrophobic residues of the αC-helix of the N-lobe. These interactions serve to stabilise the relative positions of the αC-helix and activation segment. The altered conformation of Phe-294 of PKB is correlated with the relative dispositions of its N- and C-lobes, and the disorder of the αC-helix.

[0347] Crystal structures of protein kinase-peptide substrate complexes indicate that a common function of the activation segment is to coordinate the peptide-substrate with the correct geometry to allow phosphorylation of the incoming hydroxyl-group of a Ser/Thr or Tyr residue (Knighton et al., 1991b, Bossemeyer, 1993, Hubbard, 1997; Lowe et al., 1997). In PKA, the P+1 region of the activation segment, immediately C-terminus to pThr-197, contributes to peptide binding. The conservation of the P+1 region amongst AGC-kinases, suggests that in the phosphorylated active state of a PKB-substrate complex, similar peptide-protein interactions will exist. Disorder of the activation segment of PKB in both the unphosphorylated and mono-phosphorylated (pThr-309) states will preclude interactions with protein substrates.

[0348] PKB Peptide Substrate Specificity

[0349] The substrate specificity of PKB is known from an analysis of physiological PKB phosphorylation sites, and from an oriented peptide library screen (Obata et al., 2000). PKB only phosphorylates peptides with an arginine at the P-3 position and also strongly prefers substrates with an Arg residue at P-5 and with large hydrophobic residues at P+1. The structural basis for this substrate specificity can be rationalised by comparing the ternary PKA complex with our structure of PKB including the activation segment modelled on that of PKA. Optimal peptide substrates of PKA are related, although not identical, to those of PKB and other AGC-kinases. In the ternary PKA structure, PKI has the sequence T-G-R-R-N-A-I-H, with Ala at P-0. Arg at P-3 forms a salt bridge to Glu-127 (Knighton et al., 1991b; Bossemeyer et al., 1993), and because this residue is also conserved in PKB and phosphorylase kinase (where it contacts an Arg at P-3, Lowe et al., 1997), it is likely that the equivalent interaction will be formed in PKB-peptide complexes. Interestingly, the side-chain of Tyr-330 of PKA that is directed towards the Arg P-3 residue is a glutamate in PKB, possibly enhancing the affinity for a peptide with an Arg at P-3. Unlike PKB, PKA does not have a preference for an Arg at P-5, and in the PKA structure, Arg-133 is in close proximity to the Thr side-chain at P-5 of PKI. In PKB, however, Arg-133 is replaced with a serine, and this less bulky residue would accommodate a potential interaction between the peptide Arg residue at P-5 and Glu-342 of PKB. Finally, PKB prefers bulky hydrophobic residues at P+1, in contrast to PKA which is only able to accommodate smaller aliphatic residues. This P+1 hydrophobic site is larger in PKB because the side-chain of Phe-359 lacks the hydroxyl group of the equivalent Tyr-247 residue of PKA.

[0350] Mechanism of PKB Activation by Phosphorylation

[0351] The crystal structures of PKB, combined with an analysis of the structural differences between PKB and an activated conformation of PKA, provides a framework for understanding the mechanism of activation of PKB by phosphorylation of Thr-309 and Ser-474. Central to the conversion to the activated state on phosphorylation, are concerted disorder to order transitions of the αB- and αC-helices, activation segment, and C-terminal regulatory segment, all of which are linked to conformational changes of the DFG motif and re-orientation of the N- and C-lobes to relieve steric hindrance to ATP binding, and to align catalytic site residues. Because the known structures of activated protein kinases all share the same overall features, including juxtaposition of catalytic site, and ATP and peptide binding residues, we can assume that phosphorylation of PKB converts the enzyme into a conformation similar to that of PKA phosphorylated on Thr-197. However, what distinguishes PKB from PKA, is the requirement for phosphorylation of both the C-terminal regulatory segment and the activation segment, to activate the kinase maximally. The role of Thr-309 phosphorylation will be similar to activation segment phosphorylation of PKA, CDK2 and ERK2, namely to coordinate contacts between the activation segment and other structural elements of the protein kinase, specifically, (i) the αC-helix of the N-lobe, (ii) a conserved arginine residue immediately preceding the catalytic Asp residue (Arg-165 and Asp-166, respectively of PKA), and (iii) a basic residue of the activation segment situated close to the Asp of the DFG motif (Lys-189 of PKA). Conservation of the three basic residues of PKA that contact the phosphate group of pThr-197 in all PKB-isoforms, suggests that the equivalent charge neutralisation observed in PKA will occur in the active state of PKB In all three crystal forms of PKB, which represent low and partially active forms of the enzyme, and includes pΔPH-PKB-ΔC phosphorylated on Thr-309, the activation segment is disordered, and the enzyme adopts an inactive conformation. Thus phosphorylation of Thr-309 alone is not sufficient to order the activation segment and promote an active state of the enzyme; additional phosphorylation of Ser-474 is required. The hydrophobic motif of PKA is not regulated by phosphorylation, and in the PKA crystal structure lies within a surface hydrophobic groove formed by residues whose counterparts in the αB- and αC-helices of the inactive states of PKB are disordered. The finding that the C-terminal regulatory segment, comprising the unphosphorylated hydrophobic motif of ΔPH-PKB was disordered, suggests that activation by Ser-474 phosphorylation is caused by the concomitant ordering of the regulatory segment and αB- and αC-helices mediated by the interaction of the motif with the induced N-terminal lobe surface groove. Ordering of the αC-helix will induce global changes in the PKB conformation by facilitating interactions between the residues of the αC-helix and critical regions of the molecule. These interactions include those between Lys-181 and Glu-200, and two αC-helix-activation segment interactions; His-196 and pThr-309, and hydrophobic contacts with Phe-294 of the DFG motif. Reconfiguration of the activation segment allows the correct alignment of catalytic site and substrate binding residues. Consistent with this model of activation by ordering of the regulatory segment induced by Ser-474 phosphorylation, previous studies of PKA suggested that an ordered hydrophobic motif is important for enzyme activity and stability. Replacing the conserved Phe residues of the motif with alanines, reduces catalytic activity to only 0.5% of the wild-type enzyme, and leads to decreased thermal stability (Etchebehere et al., 1997).

[0352] Allosteric Activation of pThr 309-PKB by Hydrophobic Motif Peptides

[0353] To test the model that Ser 474 phosphorylation promotes an interaction between the hydrophobic motif and the induced hydrophobic groove of the N-terminal lobe, thereby causing an allosteric activation of the kinase, the ability of peptides modelled on the hydrophobic motif of PKB to activate the enzyme via an intermolecular association with the N-terminal lobe was assessed.

[0354] First, it was shown that towards Crosstide, a peptide-substrate derived from the PKB phosphorylation site of GSK-3, the unphosphorylated form of ΔPH-PKB-ΔC has no significant catalytic activity, whereas its Thr 309 phosphorylated counterpart was active. Addition of a peptide modelled on the phosphorylated hydrophobic motif of PKBβ (HM-P, residues 460-481), activated pΔPH-PKB-ΔC, with the stimulation reaching a maximum of 4-fold at 0.6 mM, the highest concentration of HM-P peptide achievable in our assay (FIG. 5A). Significantly, this 4-fold stimulation of PKB by HM-P peptide is lower than the 7-10 fold stimulation of PKB by Ser 474 phosphorylation (Alessi et al., 1996a). Analysis of the concentration-dependent activation of PKB by HM-P (FIG. 5A) revealed that the binding sites for HM-P on ΔPH-PKB-ΔC were not fully titrated even at a peptide concentration of 0.6 mM, suggesting that higher concentrations of HM-P are necessary to fully stimulate PKB activity. The modest activation of PKB by HM-P peptide suggests a relatively low affinity of peptide for the PKB N-terminal lobe. An equivalent HM-peptide with an Asp substitution of Ser 474 was also capable of activating pΔPH-PKB-ΔC, consistent with studies showing that Asp mimics Ser 474 phosphorylation (Alessi et al., 1996a). However, the maximum activation by this peptide was only 3-fold because of the lower affinity towards ΔPH-PKB-ΔC than the HM-P peptide (FIG. 5A). Finally, the unphosphorylated HM-peptide did not stimulate PKB activity. It was also found that the phosphorylated HM-peptide did not further activate ΔPH-PKB phosphorylated on both Thr 309 and Ser 474. Furthermore, HM-P peptide was unable to activate ΔPH-PKB-ΔC with unphosphorylated Thr 309, in agreement with earlier findings that growth factor stimulation fails to activate T308A mutants of PKBa (Bellacosa et al., 1998) indicating an essential role of Thr 308/309 phosphorylation for PKB activity.

[0355] Phosphorylation of a Ser or Thr residue within the hydrophobic motif is a conserved feature of the activation of varied AGC-kinases, including PKC (Keranen et al., 1995) and the p70 and p90 S6-kinases (Pearson et al., 1995; Frodin et al., 2000). However, in some PKC isoforms, and in the PKC related kinase, PRK2, the site of Ser/Thr phosphorylation is replaced with either an Asp or Glu residue, suggesting that in these kinases, the hydrophobic motif will be constitutively activated, similarly to PKA, because of a permanent negative charge at this site. The C-terminal region of PRK2 that encompasses the carboxy-terminal hydrophobic motif was previously shown by Alessi and colleagues to interact tightly with the AGC-family kinase PDK1 (Balendran et al., 1999). PIFtide, a peptide representing the C-terminal 24 residues of PRK2, including its hydrophobic motif, was observed to stimulate PDK1 activity by four-fold (Biondi et al., 2000). Remarkably, PIFtide was found here to activate pΔPH-PKB-ΔC by 15-fold, substantially more strongly than the activation achieved by the phosphorylated HM-peptide. Analysis of the concentration dependence of pΔPH-PKB-ΔC activation by PIFtide, revealed that the peptide binds the kinase with high affinity, resulting in a maximum and saturable activation at 20 μM and a corresponding EC₅₀ value of 3 μM (FIG. 5B). Significantly, the specific activity of pΔPH-PKB-ΔC maximally activated by PIFtide was 350 nmol/min/mg, essentially identical to the specific activity of ΔPH-PKB phosphorylated on both Thr 309 and Ser 474. These specific activity data indicate that the stimulation of pΔPH-PKB-ΔC by an intermolecular association with PIFtide is equivalent to Ser 474 phosphorylation and the resultant intramolecular association between the N-lobe of PKB and phosphorylated HM and furthermore suggests that an analysis of PKB-PIFtide interactions will provide insights concerning the mechanism of activation by Ser 474 phosphorylation. PIFtide promotes a 5-fold activation of ΔPH-PKB phosphorylated on Thr 309 to a specific activity similar to that of pΔPH-PKB-ΔC. The lower level of stimulation relative to the 15-fold observed for pΔPH-PKB-ΔC can be explained by the partial phosphorylation of Ser-474 on pΔPH-PKB purified from Sf9 cells.

[0356] Using isothermal titration calorimetry, the affinity between PIFtide and both pΔPH-PKB-ΔC and ΔPH-PKB-ΔC was determined (FIG. 5C). Firstly, we found that the equilibrium dissociation constant defining the interaction between PIFtide and PΔPH-PKB-ΔC was 6 μM, essentially identical to the EC₅₀ value for the activation of pΔPH-PKB-ΔC by PIFtide (FIG. 5B). This result suggests that the association of PIFtide to PKB correlates with the activation of the kinase. Secondly, it was found that the interaction of PIFtide with ΔPH-PKB-ΔC is driven by a large negative enthalpy change (AH of −16.0 kcal.mol⁻¹) that compensates the energetically unfavourable decrease in entropy (TAS of −9.2 kcal.mol⁻¹). The observed large decrease in entropy is not generally typical of protein-peptide interactions, for example SH2-domain-phosphotyrosine peptide complexes (Ladbury et al., 1996), and is consistent with an ordering of both the protein, presumably the αB- and αC-helices of the N-lobe, and peptide on complex formation. Although PIFtide does not stimulate the activity of ΔPH-PKB-ΔC (FIG. 5B), ITC data revealing a dissociation constant of 5.5 μM indicated that PIFtide interacts with this form of the enzyme as strongly as it does to phosphorylated ΔPH-PKB-ΔC, further emphasising the crucial role of Thr 309 phosphorylation for PKB activity (FIG. 5C).

[0357] The finding that PIFtide interacts with PKB with high affinity provided a model system for testing the notion that the essential role of Ser 474 phosphorylation is to promote the association of the hydrophobic motif with the N-lobe of PKB. The residue of PIFtide equivalent to Ser 474 of PKB is an Asp, which presumably mimics a phosphorylated Ser 474 residue. To assess the importance of this residue for the ability of PIFtide to activate PKB, the concentration dependent activation of pΔPH-PKB-ΔC by PIFtide with an Ala residue substituting for the Asp was determined. Although higher concentrations of this mutant PIFtide(D−>A) are required to activate pΔPH-PKB-ΔC than wild type PIFtide, suggesting a lower affinity, the maximal activation of the kinase achieved by saturating concentrations of the mutant peptide is identical to that of the wild type peptide (FIG. 5B) The estimated EC₅₀ value for PIFtide(D−>A) is 30 μM, indicating a 10-fold lower affinity than PIFtide. ITC experiments also revealed an approximately 25-fold lower affinity between PIFtide(D−>A) and pΔPH-PKB-ΔC relative to PIFtide. Thus, these experiments demonstrate an important concept that the PIFtide-induced conformational change of pΔPH-PKB-ΔC that results when PIFtide interacts with the kinase, and which leads to a maximal stimulation of the kinase activity, does not require a negatively charged residue at the equivalent of Ser 474 of the hydrophobic motif. The major role of a negative charge at this site is to increase the association of PIFtide with the PKB N-lobe, and that other residues, particularly the conserved Phe residues of the FxxF motif (see below), are more critical for promoting the conformational change of the protein.

[0358] Because of the low affinity between pΔPH-PKB-ΔC and the PKB HM peptides, it was not possible to determine a K_(D) value defining their interaction with PKB using ITC. However, by assuming that the association between pΔPH-PKB-ΔC and the PKB HM-peptides is an equilibrium process and that at saturating concentrations of peptide, the activation of pΔPH-PKB-ΔC will be similar to that induced by PIFtide, the data in FIG. 5A were used to estimate the EC₅₀ constants for the phosphorylated and S474D HM-peptides to be 2.3 mM and 3.6 mM, respectively, an affinity ˜1000-fold lower than for PIFtide.

[0359] Mutagenesis of the Hydrophobic Motif and N-lobe Hydrophobic Groove

[0360] By assessing the ability of modified PIFtide and HM peptides to activate pΔPH-PKB-ΔC, the role of conserved residues of the hydrophobic motif (HM) to induce the active conformation of PKB was delineated. These experiments used an 11-residue peptide encompassing the six-residue hydrophobic motif of PIFtide (PIFtide1, FIG. 6A) that essentially recapitulates the activation of pΔPH-PKB-ΔC observed for the 24-residue PIFtide. The slightly lower activation suggests that residues of PIFtide N-terminal to the HM cohtribute to high affinity PKB interactions. The PKB activities were determined at PIFtide concentrations ranging from 210-250 μM, where wild-type PIFtide fully activates PKB (FIGS. 5B, 6A). While all conserved residues of the HM motif contribute to PKB activation, significantly, the two phenylalanine residues of the motif are essential for HM-induced activation. Ala substitutions of these residues in both PIFtide and the phosphorylated PKB HM-peptide, completely eliminated the potential of these peptide to stimulate PKB, even at PKB HM-peptide concentrations of 1.2 mM (FIG. 6A). A similar essential role for the equivalent Phe residues has been proposed for PKA where Ala substitutions lower the thermal stability, and virtually abolishes the catalytic activity of the enzyme (Etchebehere et al., 1997). Mutation of either the conserved Tyr residue or of both Asp residues of the PTFtide motif showed that these residues also contribute to the stimulatory affect of PIFtide on PKB activity (FIG. 6A). PIFtide activates PKB by interacting with, and simultaneously stabilising the activated conformation of PKB. Therefore, the lower stimulatory effect of mutant PIFtide and PKB peptides most likely results from a reduced affinity for the activated conformation of PKB, however, because mutant PIFtide peptides have either low or no activity even at >200 μM, we were unable to determine EC₅₀ values for their activation of PKB.

[0361] The crucial role of the conserved Phe residues of the hydrophobic motif to promote PIFtide and PKB HM-peptide mediated stimulation of PKB, and for the activity of PKA, suggests that they stabilise the active state of both PKB and PKA by a related structural mechanism. To test the notion that a hydrophobic groove is induced in PKB to engage the hydrophobic motif, and activate the kinase, a series of His tagged pΔPH-PKB-ΔC hydrophobic groove mutants was prepared and their responsiveness to PIFtide assessed. PKB mutants were transiently expressed in HEK cells, phosphorylated in vitro with PDK1, and purified using Ni-NTA agarose. SDS-PAGE and western blot analysis of the purified fractions revealed that wild type and mutant proteins were expressed to similar levels, and that the enzyme was quantitatively isolated in a phosphorylated state.

[0362] Moreover, the basal kinase activities of wild type and mutant proteins were similar, indicating that the mutations did not disrupt the overall structure of the protein. Wild type PKB prepared using this procedure was stimulated ˜5-fold by 130 μM PIFtide (FIG. 6B). The slightly lower activation probably results from incomplete Thr 309 phosphorylation, and consequently the PKB HM-peptide did not elicit measurable activation. The substitution of hydrophobic groove residues significantly reduced, but did not completely abolish the potential of PIFtide to stimulate PKB (FIG. 6B). Mutation of two αC-helix residues, Val 194 and Val 198 (Ile 85 and Leu 89 of PKA), reduced PIFtide activation to only 25% of wild type, whereas a Leu 225 mutant of the P-5 strand (Leu 116 of PKA) caused almost a complete loss of responsiveness to PIFtide (FIG. 2, 4, 6B)

[0363] Electrostatic interactions are important in defining high affinity PIFtide and PKB HM peptide associations with PKB (FIG. 5B), and form the basis for the increased affinity of the HM for the N-lobe and subsequent activation of PKB by Ser 474 phosphorylation. Examination of the PKA and PKB crystal structures suggests that Arg 202 of the αC-helix is likely to be important in mediating contacts to pSer 474 and the corresponding Asp residue of PIFtide. The equivalent residue of PKA, Arg 93, which is also conserved in PKC and PRK2, forms a water-mediated salt bridge to the carboxylate group of Glu 349 (FIG. 2). A charge reversal at this site (R202D) almost eliminates the ability of 130 pM PIFtide to activate PKB (FIG. 6B), consistent with the notion that Arg 202 forms electrostatic contacts with PIFtide. However, analogous to the finding that at high concentrations, the PIFtide(D−>A) mutant could activate PKB maximally (FIG. 5B), the R202D PKB mutant was more responsive to higher concentrations of the peptide.

[0364] Conservation of the Hydrophobic Motif Groove in AGC-Protein Kinases

[0365] The role of a phosphorylated hydrophobic motif to activate PKB that is described here, is probably applicable to other AGC-protein kinases that are regulated via dual phosphorylation of an activation segment residue and a hydrophobic motif residue, for example PKC, the p70 and p90 S6 kinases and SGK (Parekh et al., 2000; Pearson et al., 1995; Frodin et al., 2000; Kobayashi and Cohen, 1999). A disorder-order transition of PKC induced by phosphorylation is implied by the resistance of the fully phosphorylated, but not partially phosphorylated forms of PKC, to protein phosphatases, and their enhanced resistance to temperature-induced denaturation (Bornancin and Parker, 1997). Substitutions of the Phe residues of the hydrophobic motif of PKA lowers its thermal stability, and virtually abolishes its catalytic activity (Etchebehere et al., 1997). The conservation of the hydrophobic motif of AGC-kinases is correlated with the invariance of the residues equivalent to Lys-76 and Leu-116 of PKA that would be predicted to form the base of the hydrophobic groove in a number of diverse AGC-kinases, including PKA, PKB, PKC, p70-S6K, p90-S6K, SGK, NDR and PDK1. Alessi and colleagues have shown that the hydrophobic motif of PIFtide determines the ability of this peptide to bind to the N-lobe, hence activating PDK1(Balendran et al., 1999), and the presence of PIFtide greatly increases the thermal stability of PDK1(Biondi et al., 2000). By analogy to PKB, we suggest that the activation of PDK1by PIFtide involves a disorder-order transition of the αB- and αC-helices, and consequent global conformational changes.

[0366] Structure-Based Drug Design

[0367] Determination of the 3D structure of PKBβ provides important information about the binding sites of PKBβ, particularly when comparisons were made with similar enzymes. This information may then be used for rational design of PKBβ inhibitors, e.g. by computational techniques which identify possible binding ligands for the binding sites, by enabling linked-fragment approaches to drug design, and by enabling the identification and location of bound ligands using X-ray crystallographic analysis.

[0368] Since all known small molecule inhibitors of protein kinases are competitive with ATP, and therefore interact with the ATP binding site, an understanding of the PKB residues involved in the interaction with ATP enables the development of specific and potent inhibitors of this kinase. This information may thus be used to develop potent and specific small molecule inhibitors of PKB in a number of ways. PKBβ may be co-crystallised, and/or existing PKBβ crystals may be soaked, with known inhibitors of PKB, including staurosporin, and those discovered in high-throughput screening programmes known to the skilled person. Alternatively, or additionally, rational drug design programmes may make full use of the crystallographic coordinates.

[0369] Discussion and Implications for Other AGC Kinases

[0370] This study presents a model for the regulation of PKB by hydrophobic motif phosphorylation. The data indicates that the role of HM phosphorylation is to induce an ordered N-terminal lobe as a result of an increased affinity between the hydrophobic motif and the hydrophobic groove. Ordering of the αC-helix transmits a structural change to the activation segment and re-orients the N- and C-lobes. In the inactive PKB crystal structures residues of the αB- and αC-helices are disordered. Consistent with a disorder-to-order transition, the interaction of PIFtide with PKB is accompanied by a large negative entropy change. Mutation of key hydrophobic residues of the N-lobe groove and hydrophobic motif either reduce or eliminate the ability of PIFtide to activate PKB. Using PIFtide as a model system shows that the role of a negative charge within the HM (e.g. PKB Ser 474 phosphorylation) is to increase the affinity of the HM for the N-lobe. In the context of the PKB kinase domain, phosphorylation of Ser 474 will increase the ability of the HM to interact with the N-lobe via an intramolecular association. However, because PIFtide(D−>A) had only 10-fold lower affinity for PKB relative to PIFtide (FIG. 5B),-it is likely that the unphosphorylated HM of PKB will still retain a weak affinity for the N-lobe. It can therefore be rationalised why PKB mono-phosphorylated on Thr 309 has between 7-10-fold lower activity than doubly phosphorylated PKB.

[0371] Disorder to order transitions of the αC-helix as a result of phosphorylation represents a previously unrecognised mechanism for the stimulation of protein kinase activity. However, there is evidence that other AGC-kinases undergo similar transitions, modulated by the hydrophobic motif. For example, phosphorylation of the HM of PKC increases its resistance to temperature-induced denaturation (Bornancin and Parker, 1997) and the Phe residues of the PKA HM motif are critical for its stability and catalytic activity (Etchebehere et al., 1997). The conservation of the hydrophobic motif of AGC-kinases is correlated with the invariance of the residues equivalent to Lys 76 and Leu 116 of PKA predicted to form the base of the hydrophobic groove in a number of diverse ACC-kinases, (FIG. 4). Uniquely amongst AGC-kinases, PDK1 lacks a C-terminal hydrophobic motif, although its N-terminal lobe hydrophobic groove is proposed to interact with PIFtide (Biondi et al., 2000). Similarly to the findings with PKB, high affinity interactions between PIFtide and PDK1required the conserved aromatic and Asp residues of the hydrophobic motif of the peptide (Balendran et al., 1999), and were disrupted by substitutions of PDK1HM groove residues (Biondi et al., 2000).

[0372] The affinity of the HM-P peptide for PKB that is not phosphorylated on Ser 474 is −1000-fold lower than that of PIFtide, and is reminiscent of the low affinity of the tyrosine phosphorylated C-terminus of Src for its own SH2 domain, compared with optimal phosphotyrosine binding sequences (Bradshaw et al., 1998). The covalent attachment of the phosphorylated hydrophobic motif to the PKB kinase domain will greatly increase its effective concentrations presumably in excess of the EC₅₀ value estimated for the activation of PKB by the HM-P peptide. However, a modest mutual affinity may be important for two reasons. First, in order for phosphorylation of the HM to be capable of modulating its affinity for the N-lobe, the affinity of the unphosphorylated HM for the N-lobe must be sufficiently low that it is not constitutively associated with the N-lobe. For example, a substitution of PIFtide(D−>A) for the PKB HM motif would render PKB fully active and therefore unresponsive to HM phosphorylation. Second, it allows modulator proteins to gain access either to the hydrophobic groove or the phosphorylated motif, or for protein phosphatases to dephosphorylate pSer 474. Whether the activation of PKB by PIFtide reflects a biologically significant regulatory mechanism for stimulation of PKB by a modulator protein that interacts with the N-lobe is unknown. However, the affinity of PIFtide for PKB may provide insight concerning the nature of the PDK2 enzyme responsible for phosphorylating Ser 474. A possible candidate for this enzyme is a kinase that interacts with the hydrophobic binding groove of PKB, perhaps via a sequence similar to the hydrophobic motif of PKB or PIFtide.

[0373] Active Structures of PKBβ

[0374] Using the principles set out above, the present inventors generated activated conformations of PKB for use in structural studies, firstly by replacing the PKB HM with the PRK2 HM sequence, and secondly by introducing the mutation S474D into ΔPH-PKB. The resultant proteins termed PKB-PIF and PKB S474D, were expressed in Sf9 cells and phosphorylated in vitro on Thr-309 using PDK1. The phosphorylated PKB-PIF protein, has a specific activity equivalent to bis-phosphorylated (i.e. pThr-309, pSer-474) PKB, confirming that the enzyme corresponds to an activated state of the kinase.

[0375] Here is described the crystal structure of a ternary complex of the activated PKB-PIF chimera associated with a GSK-3p peptide, the first identified PKB substrate (Cross et al., 1995), and the ATP analogue AMP-PNP. The structure explains the requirement for Thr-309 phosphorylation for activity and how the PIFtide HM (as a model for Ser-474 phosphorylation) promotes the activated PKB conformation via an allosteric mechanism. Analysis of the interactions between PKB and the GSK-3β peptide explains how PKB selects for protein substrates that are distinct from those of PKA. The crystal structure of the ternary PKB S474D-GSK-3/AMP-PNP complex was found to be essentially identical to the PKB-PIF structure, demonstrating the utility of the PIFtide HM for generating activated kinase domains of AGC-protein kinases, and so further discussion centres on the PKB-PIF structure.

[0376] Results

[0377] Detailed information about the crystals, and the data collection and refinement statistics are provided in Table 2 below. TABLE 2 Crystallographic Data Collection and Refinement Statistics for Active Crystals Protein PKBβ-PIF PKBβ-S474D Amino acid residues 146-479 146-481 Phosphorylation Thr-309 Thr-309 Space group (Z) P2₁2₁2₁ (1) P2₁2₁2₁ (1) Cell parameters a (Å) 44.94 44.91 b (Å) 61.00 61.00 c (Å) 131.32 129.41 X-ray source ID14eh2 ESRF ID14eh4 ESRF Resolution (Å) 1.6 1.7 Observations (N) 150 113 116 971 Unique (N) 42 775 27 820 Completeness (%) 94.2 (88.7) 82.4 (63.7) ^(a)R_(sym) 0.052 (0.198) 0.078 (0.186) I/σI 6.1 (3.4) 6.0 (2.3) Refinement Resolution range (Å) 50-1.6 50-1.7 Reflections used (N) (%) 40 387 (83.2) 30 601 (76.5) R_(free) set (N) (%) 2 132 (4.4) 1 517 (3.8) ^(b)R_(cryst)/R_(free) 0.197/0.227 0.205/0.234 Protein atoms (N) 2 587 2 590 Solvent atoms (N) 345 280 Ligand atoms (N) 112 112 r.m.s.d. bond angles (°) 1.50 1.47 r.m.s.d. bond lengths (Å) 0.0122 0.0124

[0378] Values in parentheses are for the highest shell 1.69-1.6 Å and 1.79-1.7 Å for PKB-PIF and PKB-S474D, respectively. ^(a)R_(sym=Σ) _(h)Σ_(j)|<I(h)_(j)|/Σ_(h)Σ_(j)<I(h)>, where <I(h)>is the mean intensity of symmetry-equivalent reflections. ^(b)R_(cryst/free −Σ∥F) _(obs)|−|F_(calc)∥/Σ|F_(obs) |, where F_(obs) and F_(calc) are the observed and calculated structure factors, respectively. Root-mean-square deviations relate to the Engh and Huber parameters.

[0379] Coordinate data for the two active crystals is provided at the end of this specification as follows:

[0380] Table 6: PKB-PIF

[0381] Table 7: PKB S474D

[0382] Overall Structure of Active PKBβ Conformation, and Activation by PIFtide

[0383] The structure of the PKB-PIF ternary complex determined to 1.6 Å resolution, shown in FIG. 8, is virtually identical to the PKA ternary complex (Knighton et al., 1991b; Bossemeyer et al., 1993). Equivalent residues of the two kinases superimpose closely (r.m.s.d. 1.2 Å) with their N and C-lobes adopting similar relative orientations. The structural equivalence to the catalytic subunit of PKA, together with the presence of nucleotide and peptide substrates bound to PKB in a productive manner, indicates that the enzyme crystallised as an active enzyme-substrate complex. The activated PKB conformation differs markedly from the inactive state.

[0384] In the activated PKB-PIF structure, the αB and αC helices of the N-lobe are fully ordered, as is the activation segment and hydrophobic motif (FIG. 8). The αC helix of PKB-PIF adopts the same conformation to that seen in all other active protein kinases (Johnson et al., 1996), permitting the helix to fulfil its role to organise an active kinase structure by maintaining the nucleotide binding site and activation segment in a catalytically competent state. First, Glu-200 of the αC-helix forms a salt-bridge with Lys-181, positioning this residue to contact the β-phosphate of AMP-PNP. Second, the αC-helix contributes one of the residues (His-196) responsible for the charge neutralisation on the phosphate group of pThr-309 of the activation segment. As for the equivalent residues of PKA, pThr-309 also contacts Arg-274 of the catalytic loop and Lys-298 of the activation segment, thereby coordinating distinct regions of the structure important for configuring a kinase catalytic site (FIG. 9). Finally, the hydrophobic residues of the αC-helix interact with the aromatic side chain of Phe-294 of the DFG motif, positioning Phe-294 adjacent to the catalytic loop. The shift of conformation of Phe-294 relative to the inactive PKB state contributes to the formation of a nucleotide-binding site. In the inactive state, the altered conformation of the DFG motif causes Phe-294 to occupy the nucleotide-binding pocket, directly blocking nucleotide binding, whereas the shift in position of Asp-293 (Asp-184 of PKA), disrupts metal ion binding to the kinase catalytic site. Interactions between AMP-PNP/Mn²⁺ and the catalytic site of PKB-PIF are reminiscent of those between AMP-PNP/Mn²⁺ and PKA (FIG. 10). Specifically, the coordination of two Mn²⁺ ions and associated water molecules in the PKB structure is virtually identical to that seen in PKA. However, the adenine-binding pocket shows some differences between the two kinases, resulting in distinct protein interactions to the adenine ring and protein-bound water molecules. Such differences in protein structure will be crucial to the development of specific inhibitors of PKB.

[0385] By coordinating the phosphate group of pThr-309 via His-196, and inducing a shift in conformation of the DFG motif, the ordered αC-helix is responsible for creating a nucleotide binding site, and ordering the activation segment necessary for the generation of a catalytically competent protein kinase linked to formation of a substrate peptide binding site (see below). In the inactive conformer of mono-phosphorylated PKB, although Thr-309 is phosphorylated, disorder of the αC-helix causes a loss of contact to His-196, which together with a conformational change of the DFG motif, results in a disordered activation segment. Shifts in conformation of the αC-helix are known to be associated with the allosteric regulation of diverse kinases including CDK2 (Jeffrey et al., 1995), Src/Lck (Sicheri et al., 1997, Xu et al., 1997) and the Eph tyrosine kinase (Wybenga-Groot et al., 2001). However, the modulation of the PKB structure by a disorder to order transition of the αC helix, represents a novel mechanism for the regulation of protein kinase activity.

[0386] Hydrophobic motif peptides stimulate PKB allosterically, by promoting and stabilising the active conformation of the kinase domain characterised by ordered αB and αC helices, and activation segment. Introduction of a negative charge (either phosphoserine or an Asp amino acid) at residue 474 of the PKB HM increases its affinity for PKB. In the crystal structure of PKB-PIF, the HM of PIFtide associates within a groove in the N-lobe (FIG. 11). The groove is formed at the interface of the αB and αC helices with the β-4 and β-5 strands of the central β-sheet, and is induced by the ordered αB and αC helices. Extensive hydrophobic contacts between the invariant aromatic side-chains of Phe-470 and Phe-473 of the HM motif and hydrophobic residues of the αB and αC helices and β-5 strand, essentially equivalent to those observed in PKA (Phe-347 and Phe-350), function to stabilise the ordered αB and αC helices. The critical structural role the HM Phe residues perform to promote ordered αB and αC helices explains the finding that their replacement by Ala completely eliminates the ability of PIFtide and PKB HM peptides to stimulate PKB. Similarly, in PKA the equivalent Phe residues are also essential for its stability and catalytic activity (Etchebehere et al., 1997). The C-terminus of the HM of PKB extends relative to its counterpart in PKA where Phe-350 corresponds to the C-terminal residue of the catalytic subunit and probably contributes to a correctly positioned and ordered αC-helix. In PKB, residues Tyr-475 to Trp-479 pack against the C-terminus of the αC helix and form an edge P-strand of the central β-sheet. The aromatic side chain of the invariant Tyr-475 residue of the HM motif packs against Leu-215, whereas its hydroxyl group forms a hydrogen bond to the side chain of Arg-208. The conservation of these two αC-helix residues suggests that similar interactions will occur between the HM Tyr residue and αC-helix in other AGC kinases.

[0387] An Asp residue mimics the property of Ser-474 phosphorylation to activate PKB Substitution of Ala for Asp at the equivalent position of the HM of PIFtide reduced the affinity of the mutant PIFtide for PKB by 10-fold, suggesting that the role of a negative charge at this position (either phosphoserine or Asp) is to promote the association of the HM to the N-terminal lobe, concomitantly activating the kinase In the electron density map, the side chain for Asp-474 is well ordered, however, slightly contrary to our expectations, the Asp carboxylate group does not form salt bridges with basic residues of the protein. Three contacts with the protein are formed, however. First, a hydrogen bond (3.0 Å) is accepted from the amide side chain of Gln-220 of the β-4 strand. Second, a water-mediated contact is formed to the main-chain amide group of Gln 220. Thirdly, and intriguingly, a van der waals contact (3.5 Å) is made between the OD1 atom of Asp-474 and the edge hydrogen atom of the HM Phe-473 aromatic ring. The geometry of this interaction, where the OD1 atom of Asp-474 is in plane with the aromatic ring of Phe-473, suggests that this interaction would be energetically stable and may therefore contribute to the favourable interaction between the PIFtide HM and PKB by stabilising the appropriate conformation of the Phe-473 side chain allowing it to engage the N-lobe hydrophobic groove. PIFtide associates with PKB 1000-fold more tightly that the authentic PKB HM. One possible explanation is that Asp-472 of the PIF HM (Gln in PKB) forms a salt-bridge with Arg 202 of the αC-helix, similar to that between Glu-349 and Arg-93 of PKA, whereas Asp-478 accepts a hydrogen bond from Arg-208. In addition Trp-479 (Ile in PKB) forms extended hydrophobic contacts with Ala-214 and Lys-216 of the αC-helix (FIG. 11)

[0388] Protein-Peptide Interactions

[0389] The substrate specificity of PKB is known from an analysis of physiological PKB phosphorylation sites, and from an oriented peptide library screen (Alessi et al., 1996b; Obata et al., 2000). PKB only phosphorylates peptides with arginine residues at the P−3 and P−5 positions, and also strongly prefers substrates with a large hydrophobic residue at P+1 and a Thr at P−2. Optimal peptide substrates of PKB are related, although not identical, to other AGC-kinases. PKA for example, phosphorylates peptides with smaller aliphatic residues at P+1, and basic residues at P−3 and P−2 (Kennelly and Krebs, 1991). The structural basis for this substrate specificity can be rationalised by comparing the ternary PKA complex with our structure of PKB in complex with residues 3-12 of GSK-3β. Similarly to other protein kinases, the substrate peptide binding site is centred on the activation segment, with main-chain amide and carbonyl groups of residues P+1 to P+3 of the peptide forming a two-stranded anti-parallel β-sheet with residues of the P+1 site of the activation segment (Cys-311 and Gly-312). The side-chain of Arg at P-3 of the GSK-3 peptide forms a bidendate salt bridge to Glu-236 of PKB, identical to that seen in the PKA and phosphorylase kinase-peptide complexes. (Knighton et al., 1991b; Lowe et al., 1997). Also similar to PKA, Asp-440 accepts a long (4 Å) hydrogen bond from the quanidinium group of Arg at P−3. Unlike PKB however, PKA does not have a preference for an Arg at P−5, and in the PKA structure, Arg-133 is in close proximity to the Thr side-chain at P−5 of PKI, suggesting that a peptide with Arg at P−5 would be excluded. In contrast, the residue equivalent to Arg-133 is a serine in PKB and this less bulky residue allows the interaction of the peptide Arg residue at P−5 with Glu-279 and Glu-342. Interestingly, the guanidinium group of Arg at P−5 of the GSK-3 peptide bound to PKB adopts a similar position to the guanidinium group of an Arg at P−2 of the PKI peptide bound to PKA, suggesting that a peptide with Arg residues at both P−2 and P−5 could not bind to PKB. Thr (P−1) is solvent exposed, however the hydroxyl group of the Thr (P−2) side chain donates a hydrogen bond to the carboxylate group of Glu-279, which in turn contacts Arg at (P−5), explaining the preference of a peptide for Thr at P−2 (Alessi et al., 1996a, Obata et al., 2000). Finally, the bulky hydrophobic Phe residue at P+1 of the peptide is accommodated within an enlarged P+1 pocket resulting from the presence of a Phe at residue 359 compared with a Tyr in the equivalent position of PKA.

[0390] Interactions between the catalytic domain and the nucleotide analogue AMP-PNP, the substrate peptide GSK-3, and between the catalytic domain and PIFtide are detailed in the following Tables 3 to 5 respectively. TABLE 3 List of contacts between PKB-PIF and AMP-PNP PKB-PIF atoms AMP-PNP atoms distance Å Gly 159A CA AMP-PNP 500B O4* 3.70 Val 166A CB AMP-PNP 500B O4* 3.52 Val 166A CG1 AMP-PNP 500B N9 3.81 Val 166A CG2 AMP-PNP 500B O5* 3.35 AMP-PNP 500B C5* 3.89 AMP-PNP 500B O4* 3.37 Ala 179A CB AMP-PNP 500B N6 3.78 AMP-PNP 500B C6 3.60 AMP-PNP 500B N1 3.50 Lys 181A CD AMP-PNP 500B O1A 3.58 Lys 181A CE AMP-PNP 500B O2B 3.81 AMP-PNP 500B O1A 3.33 AMP-PNP 500B O3A 3.67 Lys 181A NZ AMP-PNP 500B O2B 3.01*** AMP-PNP 500B PB 3.81 AMP-PNP 500B O1A 2.83*** AMP-PNP 500B O3A 3.57* AMP-PNP 500B PA 3.75 Thr 213A CG2 AMP-PNP 500B N6 3.63 Met 229A SD AMP-PNP 500B N6 3.86 Met 229A CE AMP-PNP 500B N7 3.48 AMP-PNP 500B N6 3.74 Glu 230A O AMP-PNP 500B N6 3.01*** Tyr 231A CD1 AMP-PNP 500B C2 3.88 Ala 232A N AMP-PNP 500B N1 3.20*** AMP-PNP 500B C2 3.75 Ala 232A CB AMP-PNP 500B N1 3.76 Glu 236A CG AMP-PNP 500B O2* 3.31 Glu 236A CD AMP-PNP 500B O2* 3.33 Glu 236A OE2 AMP-PNP 500B C3* 3.76 AMP-PNP 500B O3* 2.94*** AMP-PNP 500B C2* 3.63 AMP-PNP 500B O2* 2.61*** Asp 275A OD2 AMP-PNP 500B O2G 3.82* Lys 277A CE AMP-PNP 500B O2G 3.12 Lys 277A NZ AMP-PNP 500B O2G 2.89*** Glu 279A C AMP-PNP 500B O3* 3.76 Glu 279A O AMP-PNP 500B C3* 3.62 AMP-PNP 500B O3* 2.78*** Asn 280A OD1 AMP-PNP 500B O2G 3.70* AMP-PNP 500B O2A 3.42* Met 282A SD AMP-PNP 500B C2* 3.84 Met 282A CE AMP-PNP 500B C2* 3.77 AMP-PNP 500B O2* 3.90 AMP-PNP 500B C2 3.76 AMP-PNP 500B N3 3.31 AMP-PNP 500B C4 3.71 Thr 292A CB AMP-PNP 500B N7 3.66 Thr 292A OG1 AMP-PNP 500B C8 3.65 AMP-PNP 500B N7 2.84*** AMP-PNP 500B C5 3.72 AMP-PNP 500B N6 3.84* Thr 292A CG2 AMP-PNP 500B C8 3.70 AMP-PNP 500B N7 3.62 Asp 293A CA AMP-PNP 500B O1A 3.79 Asp 293A CB AMP-PNP 500B O1A 3.37 AMP-PNP 500B PA 3.82 AMP-PNP 500B O2A 3.29 Asp 293A CG AMP-PNP 500B O2B 3.18 AMP-PNP 500B O1A 3.59 AMP-PNP 500B PA 3.81 AMP-PNP 500B O2A 3.31 Asp 293A OD1 AMP-PNP 500B O2B 2.98*** Asp 293A OD2 AMP-PNP 500B O1G 3.24*** AMP-PNP 500B O2B 3.05*** AMP-PNP 500B PG 3.47 AMP-PNP 500B N3B 3.53* AMP-PNP 500B O2G 3.07*** AMP-PNP 500B PB 3.79 AMP-PNP 500B PA 3.86 AMP-PNP 500B O2A 3.02*** Phe 439A CE2 AMP-PNP 500B N3 3.49 Phe 439A CZ AMP-PNP 500B C2 3.78 AMP-PNP 500B N3 3.75

[0391] Contacts listed if less than 3.9 Å between AMP-PNP and PKB-PIF TABLE 4 List of contacts between PKB-PIF and GSK-3 GSK-3 atoms PKB-PIF atoms distance Å Arg 4C CD Glu 342A OE2 3.50 Phe 238A CE1 3.77 Arg 4C NE Glu 342A OE2 2.88*** Arg 4C CZ Tyr 316A OH 3.81 Glu 342A OE2 3.82 Phe 238A CE1 3.77 Glu 279A OE2 3.57 Arg 4C NH1 Glu 279A CD 3.80 Phe 238A CD1 3.89 Phe 238A CE1 3.22 Phe 238A CZ 3.37 Glu 279A OE2 2.95*** Arg 4C NH2 Glu 279A CD 3.51 Glu 279A OE1 3.05*** Tyr 316A CE1 3.30 Tyr 316A CZ 3.47 Tyr 316A OH 2.78*** Glu 279A OE2 3.28*** Arg 4C O Phe 238A CZ 3.44 Pro 5C CD Tyr 351A OH 3.87 Pro 5C CG Tyr 351A OH 3.75 Arg 6C CA Glu 279A OE2 3.65 Arg 6C CG Phe 238A CE2 3.72 Arg 6C CD Phe 443A CE1 3.88 Phe 443A CZ 3.65 Arg 6C NE Phe 443A CZ 3.77 Arg 6C CZ Glu 279A CG 3.87 Glu 236A OE2 3.39 Glu 236A OE1 3.83 Arg 6C NH1 Phe 238A CD2 3.79 Glu 236A CD 3.35 Glu 236A OE2 3.08*** Glu 236A OE1 2.86*** Arg 6C NH2 Glu 279A CB 3.82 Glu 279A CG 3.63 Glu 236A CD 3.76 Glu 236A OE2 2.83*** Arg 6C C Glu 279A OE2 3.72 Thr 7C N Glu 279A OE2 2.84*** Thr 7C CA Glu 279A OE2 3.70 Thr 7C CB Glu 315A OE1 3.62 Thr 313A CG2 3.56 Glu 279A OE2 3.67 Thr 7C OG1 Lys 277A CD 3.64 Glu 279A CD 3.34 Glu 279A OE1 3.27*** Thr 313A CG2 3.47 Glu 279A OE2 2.93*** Thr 7C CG2 Glu 315A CD 3.68 Glu 315A OE1 3.41 Thr 7C C Lys 277A NZ 3.69 Thr 7C O Lys 277A NZ 2.98*** Glu 279A OE2 3.83* Thr 8C CA Lys 277A NZ 3.80 Thr 8C C Thr 313A OG1 3.89 Lys 277A NZ 3.73 Thr 8C O Pro 314A CD 3.39 Thr 313A OG1 3.88* Thr 313A CG2 3.72 Ser 9C N Thr 313A OG1 3.72* Lys 277A NZ 3.54* Ser 9C CA Gly 312A O 3.23 Thr 313A OG1 3.50 Ser 9C CB Asp 275A OD2 3.65 Gly 312A O 3.41 Thr 313A OG1 3.58 Ser 9C C Gly 312A O 3.54 Phe 10C  N Gly 312A O 2.90*** Phe 10C  CD2 Pro 314A CD 3.75 Gly 312A C 3.85 Gly 312A O 3.14 Phe 10C  CE1 Phe 310A CE1 3.85 Phe 310A CD1 3.84 Phe 310A O 3.59 Phe 10C  CE2 Leu 317A CD1 3.85 Gly 312A C 3.83 Gly 312A O 3.55 Phe 10C  CZ Leu 317A CD1 3.78 Phe 10C  O Cys 311A CA 3.42 Cys 311A CB 3.32 Cys 311A C 3.86 Gly 312A N 3.25*** Leu 296A CD1 3.70 Gly 312A O 3.48* Ala 11C  CA Phe 310A 0 3.79 Ala 11C  CB Glu 193A CD 3.84 Glu 193A OE1 3.48 Glu 193A OE2 3.71 Ala 11C  C Phe 310A O 3.90 Glu 12C  N Phe 310A O 3.05*** Glu 12C  CB Phe 310A O 3.55 Glu 12C  OE1 Phe 310A CB 3.89 Glu 12C  OE2 Phe 310A CD1 3.56

[0392] Contacts listed if less than 3.9 Å between GSK-3 peptide and PKB-PIF TABLE 5 List of contacts between catalytic domain of PKB-PIF and PIFtide PIFtide atoms PKB-PIF atoms distance Å Met 469A CG Val 194A CG1 3.89 Met 469A CE Ile 189A CD1 3.75 Phe 470A CB Gln 220A OE1 3.60 Gln 220A NE2 3.64 Phe 470A CE1 Val 194A CG1 3.78 Leu 225A CD1 3.71 Phe 470A O Gln 220A NE2 2.92*** Asp 472A O Gln 205A NE2 3.03*** Asp 472A OD2 Arg 202A NH2 2.47*** Phe 473A CA Ser 201A OG 3.75 Phe 473A CD1 Ser 201A CB 3.79 Phe 473A CE1 Phe 227A CE2 3.79 Phe 227A CZ 3.60 Phe 473A CE2 Phe 219A O 3.42 Leu 225A CD2 3.85 Cys 226A O 3.73 Phe 473A CZ Leu 225A CD2 3.85 Leu 225A CB 3.74 Phe 227A CE2 3.75 Phe 227A CZ 3.66 Phe 473A C Ser 201A OG 3.64 Phe 473A O Ser 201A OG 2.77*** Gln 205A NE2 3.30*** Ala 218A CB 3.38 Asp 474A CA Ala 218A O 3.34 Asp 474A CG Gln 220A NE2 3.90 Asp 474A OD1 Gln 220A NE2 3.33* Gln 220A N 3.84* Gln 220A CG 3.64 Phe 219A CA 3.69 Ala 218A O 3.80* Asp 474A C Ala 218A O 3.63 Tyr 475A N Ala 218A CB 3.82 Ala 218A O 2.96*** Tyr 475A CB Gln 205A CG 3.83 Gln 205A CD 3.86 Ala 218A CB 3.86 Tyr 475A CG Gln 205A CG 3.67 Tyr 475A CD1 Gln 205A CG 3.84 Gln 205A OE1 3.88 Tyr 475A CD2 Leu 215A CD2 3.66 Tyr 475A CE2 Leu 215A O 3.56 Tyr 475A OH Gln 205A O 3.66* Arg 208A NH2 3.12*** Arg 208A CZ 3.65 Arg 208A NH1 3.54* Tyr 475A O Tyr 217A CA 3.43 Tyr 217A C 3.67 Ala 218A N 2.97*** Ala 218A O 3.34* Ile 476A C Lys 216A O 3.88 Ala 477A N Lys 216A O 2.98*** Ala 477A CA Lys 216A O 3.71 Ala 477A CB Leu 215A O 3.67 Lys 216A O 3.25 Asp 478A OD1 Arg 208A NH2 3.12*** Trp 479A CE2 Leu 215A O 3.87 Trp 479A NE1 Leu 215A O 3.70* Trp 479A CZ2 Leu 215A C 3.81 Ala 214A CB 3.74 Leu 215A O 3.50 Trp 479A C Lys 216A NZ 3.60 Trp 479A O Lys 216A NZ 3.73* Trp 479A OXT Lys 216A CE 3.82 Lys 216A NZ 2.74***

[0393] Contacts listed if less than 3.9 Å between PIFtide and catalytic domain of PKB-PIF

[0394] Materials and Methods

[0395] The Genebank accession numbers for the PKB isoforms are as follows: α gi 190827 (m63167); β gi 178325 (m95936); γ gi 4757578 (af124141)

[0396] Expression of ΔPH-PKBβ-ΔC (residues 146-460) and ΔPH-PKBfl (residues 146-481)

[0397] Generation of recombinant baculovirus using the GIBCO/Life Sciences Bacmid system was performed using standard procedures.

[0398] For ΔPH-PKBβ-ΔC, 3 PCR reactions were set up as follows: 36.5 μl H₂O 5 μl 10x pfu buffer 5 μl dNTPs 0.2 mM 1.5 μl 5′ Primer 36117 60 pmols 1 μl 3′ Primer 36508 60 pmols 1 μl PfastBacHTa ΔPH PKBβ 2851a (170 ng) 50 μl total + 2.5 u pfu

[0399] Pfu polymerase and buffer were purchased from Promega (M7741). All PCR reactions were performed in a Perkin Elmer Geneamp PCR system 9700.

[0400] PCR conditions 60 s at 95° C.,

[0401] then 15 cycles:

[0402] 60 s at 95° C.

[0403] 120 s at annealing temperature ₆₂° C.

[0404] 180 s at 72° C.

[0405] Primers were:

[0406] 36117: GCC ATG GAT CCG AAA GTG ACC ATG AAT GAC TTC (5′ BamHI)

[0407] 36508: GGG GGT ACC TCA CAG GCT GTC ATA GCG GTC AGG (3′ KpnI)

[0408] For ΔPH-PKBβ, 3 PCR reactions were set up as follows: 37 μl H₂O 5 μl 10x pfu buffer 5 μl dNTPs 2.5 mM 1 μl 5′ Primer 36117 70 pmols 1 μl 3′ Primer 28585 54 pmols 1 μl pFastBacHTa.ΔPH PKBβ 2702b (200 ng) 50 μl total + 2.5 u pfu

[0409] Pfu polymerase and buffer were purchased from Promega (M7741). All PCR reactions were performed in a Perkin Elmer Geneamp PCR system 9700

[0410] PCR conditions 60 s at 95° C.,

[0411] then 15 cycles:

[0412] 60 s at 95° C.

[0413] 120 s at annealing temperature 66° C.

[0414] 180 s at 72° C.

[0415] Primers were: 36117: GCC ATG GAT CCG AAA GTG ACC ATG AAT GAC TTC (5′ BamHI) 28585: GGG GGT ACC TCA CTC GCG GAT GCT GGC CGA GTA GG (3′ KpnI)

[0416] All PCR fragments were pooled and purified using the Qiagen PCR purification kit (28106) and digested with the appropriate restriction enzymes and subcloned into the pFastBacHTa (10584-027) vector from Gibco BRL life technologies.

[0417] Ligation mixes were used to transform E. coli XLl blue (Stratagene) and colonies containing recombinant DNA were grown up for miniprep DNA analysis. Miniprep was prepared using Qiagen miniprep kit 27106. All expression constructs were fully sequenced on an Applied Biosystems 3700 automated sequencer.

[0418] Insect cells (density ˜2.0×10⁶ cells/ml, total volume of 2.7 L; 5.4×10⁹ Sf9 cells), grown in a culture of GIBCO/Life Sciences supplemented Sf9001I medium were infected at a moiety of infection of 2 and grown for 72 hours prior to harvesting.

[0419] Purification of ΔPH-PKBβ/-ΔC (residues 146-460) and ΔPH-PKBβ (residues 146-481)

[0420] All procedures were performed at 4° C.

[0421] 1. Cell lysis: Insect cells were lysed in a Q-sepharose buffer A (25 mM Tris.HCl, [pH 7.5], 25 mM NaCl, 25 mM NaF, 25 mM β-glycerophosphate, 0.1% (v/v) β-mercaptoethanol, 2 mM benzamidine, 0.2 mM PMSF, 10% (v/v) glycerol, 1 μg/ml of DNAase.

[0422] 2. Q-sepharose, anion exchange chromatography: The lysate was cleared by centrifugation and loaded onto a 50 mL Q-sepharose column equilibrated in buffer A. The column was washed in 200 mL of buffer A and PKB was eluted using 100 mL of buffer A+1 M NaCl.

[0423] 3. Ni-NTA affinity chromatography: The pH of the eluate was raised to 8.0 using a 1 M of Tris.HCl (pH 9.2) and this sample was loaded onto a Ni-NTA agarose column containing 10 mL of Ni-NTA agarose resin that had been pre-equilibrated in buffer B: 20 mM imidazole, 20 mM Tris.HCl (pH 8.0), 25 mM NaF, 25 mM β-glycerophosphate, 500 mM NaCl, 0.1% (v/v) P-mercaptoethanol, 2 mM benzamidine, 0.2 mM PMSF. The column was washed and the protein was eluted using buffer B+300 mM imidazole. EDTA and DTT to final concentrations of 0.5 mM and 2 mM, respectively, were added immediately to the eluted protein. Phosphorylation reactions (see below) were performed after this step.

[0424] 4. Phenyl TSK hydrophobic interaction chromatography: The protein was brought to the appropriate concentration of ammonium sulphate and loaded onto a phenyl TSK column equilibrated in buffer C: 50 mM Tris.HCl (pH 7.5), 100 mM NaCl, 2 mM DTT, 2 mM benzamidine, 0.2 mM PMSF, with the same concentration of ammonium sulphate as the protein solution. The column was washed and PKB was eluted using a linear gradient developed to a buffer D consisting of 50 mM Tris.HCl (pH 7.5), 100 mM NaCl, 15% (v/v) glycerol, 2 mM DTT, 2 mm benzamidine, 0.2 mM PMSF.

[0425] Concentrations of ammonium sulphate used were as follows: pΔPH-PKBβ-ΔC 1.23 M ammonium sulphate ΔPH-PKBβ-ΔC 0.63-0.68 M ammonium sulphate ΔPH-PKBβ 0.82-0.86 M ammonium sulphate

[0426] Following this HIC step, those proteins which were to be dephosphorylated were treated with λ protein phosphatase, as described below.

[0427] 5. Tev protease cleavage. The 6×His affinity tag was removed by cleavage using Tev (tobacco etch virus) protease. Tev protease was added to PKB from step 4 and this solution was dialysed over 14 hr into buffer E: 50 mM Tris.HCl (pH 8.0), 100 mM NaCl, 5 mM DTT.

[0428] 6. To remove Tev protease (as well as PDK1 and λ protein phosphatase, where appropriate) from PKB after cleavage of the His-tag from PKB, the solution of Tev protease and PKB were dialysed into buffer B: 20 mM imidazole, 20 mM Tris.HCl (pH 8.0), 25 mM NaF, 25 mM β-glycerophosphate, 500 mM NaCl, 0.1% (v/v) β-mercaptoethanol, 2 mM benzamidine, 0.2 mM PMSF and loaded onto a Ni-NTA agarose column. Cleaved PKB was recovered in the flow through.

[0429] 7. Q-sepharose, anion exchange chromatography. The PKB collected in step 6 was dialysed into Q-sepharose buffer F: 25 mM Tris.HCl (pH 7.5), 25 mM NaCl, 5% (v/v) glycerol, 0.5 mM EDTA, 2 mM DTT, 0.2 mM PMSF. The column was washed in the above buffer and the protein was eluted by developing a shallow gradient to buffer F+0.5 M NaCl.

[0430] 8. Size exclusion chromatography. The protein from step 7 was concentrated to <2 mL and loaded onto an S75 gel filtration column equilibrated in buffer G: 10 mM Tris.HCl (pH 7.5), 100 mM NaCl, 2 mM DTT.

[0431] Expression of PDK1

[0432] Recombinant PDK1, for phosphorylation of ΔPH-PKβ-ΔC, was expressed from recombinant baculovirus generated by standard procedures.

[0433] 3 PCR reactions were set up as follows using pCMV5.myc PDK1fl-1 (Pullen et al., 1998) as a template: 23 μl H₂O 5 μl 10x Taq buffer 10 μl Q-solution (5x) 5 μl dNTPs 0.25 mM 4 μl 5′ Primer 30665 60 pmols 1 μl 3′ Primer 22777 60 pmols 2 μl pCMV5.myc PDK1 fl-1 (200 ng) 50 μl total + 2.5 u pfu

[0434] Taq polymerase, Q-solution and buffer were purchased from Qiagen 201203. All PCR reactions were performed in a Perkin Elmer Geneamp PCR system 9700 PCR conditions 60 s at 94° C., Then 5 cycles: 30 s at 94° C. 4 min at 72° C. then 5 cycles: 30s at 94° C. 4 min at 70° C. then 20 cycles: 30s at 94° C. 4 min at 68° C.

[0435] Primers 30665 CCT GCT AGC ACG GCC ACG ACC ACC AGC CAG CTG TAT GAC NheI 22777 CCC GAA TTC TCA CTG CAC AGC GGC GTC CGG GTG GC EcoRI

[0436] All PCR fragments were pooled and purified using the Qiagen PCR purification kit (28106) and digested with the appropriate restriction enzymes and subcloned into the vectors indicated below. The PCR fragment was subcloned into pRSETA as a NheI/KpnI fragment, subsequently released as a NdeI/KpnI fragment and subcloned into pFastBac1 (10360-014 from Gibco BRL life technologies) between the BamHI and KpnI sites using a BamHI-NdeI linker.

[0437] All PCR fragments were pooled and purified using the Qiagen PCR purification kit (28106) and digested with the appropriate restriction enzymes and subcloned into pFastBacl (10360-014) from Gibco BRL life technologies to yield pFastbacl.His PDK1- c(full length aa 1-556).

[0438] Ligation mixes were used to transform E. coli XL1 blue (Stratagene) and colonies containing recombinant DNA were grown up for miniprep analysis.

[0439] Miniprep was prepared using Qiagen miniprep kit 27106. All expression constructs were fully sequenced on Applied Biosystems 3700.

[0440] Insect cells (density ˜2.0×10⁶ cells/ml, total volume of 2.7 L; 5.4×10⁹ Sf9 cells), grown in a culture of GIBCO/Life Sciences supplemented Sf9001I medium were infected at a moiety of infection of 2 and grown for 72 hours prior to harvesting.

[0441] Purification of PDK1

[0442] PDK1 was purified by following steps 1, 2, 3 5 and 6 described above, as for recombinant PKB.

[0443] Phosphorylation of ΔPH-PKBβ-ΔC (residues 146-460) and ΔPH-PKBβ (residues 146-481) on Thr309 Using PDK1

[0444] PKB from step 3 above was dialysed into a buffer containing 50 mM Tris.HCl (pH 7.5), 100 mM NaCl, 5 mM DTT. MgCl₂ and ATP were added to a final concentration of 5 mM. PDK1was added and the mixture was incubated at 4° C. for 14 hrs and at 20° C. for 2 hrs. PDK1was removed from phosphorylated PKB by Ni-NTA agarose. The PKB-PDK1 solution was dialysed into buffer B (step 3) and loaded onto Ni-NTA agarose and eluted as described in step 3. The phosphorylated PKB was further purified using steps 4-8 above.

[0445] Dephosphorylation of ΔPH-PKBβ (residues 146-481) using λ Protein Phosphatase

[0446] ΔPH-PKBβ (residues 146-481) was dialysed into the following buffer: 50 mM Tris.HCl (pH 7.5), 150 mM NaCl, 2 mM MnCl2, 5 mM DTT, λ protein phosphatase was added at a ratio of 1 mg of λ protein phosphatase to 8 mg of ΔPH-PKBβ. ΔPH-PKBβ was incubated in these conditions at 20° C. for 2 h. Simultaneously, TEV protease was added to cleave the N-terminal His tag. After 2 h ΔPH-PKBβ was dialysed into buffer B (step 3) and loaded onto a Ni-NTA column to remove λ phosphatase and TEV. PKB was collected in the flow through. The protein was further purified using Q-sepharose and gel filtration chromatography (steps 7 and 8).

[0447] Crystallisation of pΔPH-PKBβ-ΔC (residues 146-460)—First Batch.

[0448] The protein was concentrated to 10 mg/ml and AMPPNP/MgCl₂ was added to a final concentration of 5 mM. Crystals were grown using the under-oil batch method. A small volume of protein (3 μl) was mixed with an equal volume of crystallisation buffer: 30% (w/v) polyethylene glycol 4000, 0.2 M lithium sulphate, 0.1 M Tris.HCl (pH 7.5), 5 mM DTT, within individual wells of a 72 well polystyrene tray (Nunc) and immersed under 5 ml of silicone oil. The trays were incubated at 20° C. and crystals appeared within a few days and grew to a maximum size of 0.1 mm×0.1 mm×0.5 mm in a week. The crystals exhibited a rod-like rectangular morphology.

[0449] Crystallisation of PΔPH-PKB-ΔC (second batch), ΔPH-PKB-ΔC, and ΔPH-PKB.

[0450] The protein was concentrated to 10 mg/ml and AMP-PNP/MgCl₂ was added to a final concentration of 5 mM. Crystals were grown using the under-oil batch method. A small volume of protein (1 μl) was mixed with an equal volume of crystallisation buffer: 30% (w/v) polyethylene glycol 4000, 0.2 M lithium sulphate, 0.1 M Tris.HCl (pH 8.5), 5 mM DTT, within individual wells of a 72 well polystyrene tray and immersed under silicone oil and incubated at 20° C.

[0451] Data Collection and Structure Determination

[0452] Preparation of Crystals for X-Ray Data Collection:

[0453] Crystals were harvested from the crystallisation trays and incubated in a cryoprotection buffer consisting of 18% (w/v) polyethylene glycol 4000, 120 mM lithium sulphate, 60 mM Tris.HCl (pH 7.5), 15% (v/v) polyethylene glycol 400, 5 mM AMPPNP/MgCl₂ for 20 secs, prior to mounting the crystals in a ryan loop, and freezing in a nitrogen gas stream at 100 K. X-ray diffraction data were collected at the SRS, Daresbury, UK and at the European Synchrotron Radiation Facility, Grenoble, France.

[0454] Data were collected and these were analysed and processed using the HKL (Otwinowski and Minor, 1997) and CCP4 (CCP4, 1994) program suites. The structure was solved by means of molecular replacement using the coordinates of the ternary complex of the catalytic subunit of murine PKA as a search model (Knighton et al., 1991) with the program CNS (Brunger et al., 1998). The atomic structure was refined using rigid body and least squares refinement with CNS. Model building and analysis was done using 0 (Jones et al., 1991).

[0455] Protein Kinase B Assay

[0456] PKB was assayed essentially as described by Andjelkovic et al. (1999) with 30 μM Crosstide (GRPRTSSAEG) as substrate except the protein kinase A inhibitor peptide was not added to the reactions. For peptide stimulation experiments the various peptides were dissolved in water and added to the kinase assay mix prior to adding the PKB protein. Peptides were synthesized by Franz Fischer at the FMI or purchased from Neosystem, Strasburg, France.

[0457] Peptides Used Were: PKB HM-P GLLELDQRTHFPQFpSYSASIRE PKB HM-D GLLELDQRTHFPQFDYSASIRE PKB HM-S GLLELDQRTHFPQFSYSASIRE PKB HM-PF GLLELDQRTHAPQApSYSASIRE PIFtide REPRILSEEEQEMFRDFDYIADW PIFtide (D->A) REPRILSEEEQEMFRDFAYIADW PIFtide1             MFRDFDYIADW PIFtide2             MFRDFAYIADW PIFtide3             MFRAFAYIADW PIFtide4             MARDADYIADW PIFtide5             MFRDFDAIADW

[0458] pS is used to indicate phosphoserine.

[0459] All experiments were performed in either duplicate or triplicate.

[0460] Generation of PKBβ-PIF Chimera

[0461] A PKBβ kinase domain was generated with the PIFtide replacing the HM phosphorylation site (C-terminal sequence that encompasses residues 146 to 467 of the kinase attached to PIF as indicated below 146KVTMNDF......GLLELDQR467 EEQEMFRDFDYIADW          PKB                       PIF

[0462] To prepare the plasmid expression construct encoding the chimeric protein a 3′ oligonucleotide covering this region was synthesised with a Kpn1 site. The 5′ oligonucleotide used covered the region of PKB encoding 146 KVTMNDF region with a BamH1 site for subcloning into pFastBac HTa.

[0463] The sequence of the 5 prime oligonucleotide is:

[0464] gec atg gat ccg aaa ctg acc atg aat gac ttc (33mer ID36117).

[0465] The sequence of the 3 prime oligonucleotide is: ggg ggt acc tca cca gtc ggc gat gta gtc gaa gtc gcg gaa cat ctc ctg ctc ctc ccg ctg gtc cag ctc cag taa gcc (81mer ID 38408).

[0466] For the PCR we carried 3 reactions with the following additions:

[0467] 1 μl 200 ng Template (pFastBac HTaAPH PKBβ 2851a)

[0468] 5 μl Qiagen Taq X10 buffer

[0469] 10 μl Q solution (for difficult templates)

[0470] 5 μl deoxynucleotide mixture (2.5 mM of dATP, dCTP, dGTP and TTP)

[0471] 24 μl ddH₂O

[0472] 1 μl oligonucleotide 36117 (60 picomoles)

[0473] 4 μl oligonucleotide 38408 (60 picomoles)

[0474] 1 μl 2.5 U Taq polymerase (Qiagen) and 0.2U Pfu (Promega)

[0475] Touchdown PCR was performed as follows: 1 minute at 94° C.; 5 cycles of 94° C. for 30 sec. followed by 72° C. for 4 minutes; 5 cycles of 94° C. for 30 sec. followed by 4 minutes at 70° C.; 15 cycles of 94° C. for 30 sec. followed by 4 minutes at 68° C. After the final cycle the PCR reaction was incubated for 10 minutes at 68° C. and stored at 4° C.

[0476] The PCR products are purified on Qiagen Qiaquick PCR purification columns and eluted in 50 μl ddH₂O. Purified PCR products are digested with BamHI (20 units) and KpnI (20 units) at 37° C. for 2 hrs. The digested PCR product is purified by electrophoresis using 1% Agarose gel run in Tris-Acetate buffer (TAE).

[0477] Purified DNA was isolated from the 1% Agarose gel using a Qiagen gel extraction kit following the manufacturers protocol and subcloned.

[0478] The vector pFastBac HTa (Gibco/Invitrogen) digested with BamHI/KpnI was used to subclone the PCR fragment. The sequence of the PCR product was determined using an Applied Biosystem DNA Analyzer 3700.

[0479] The pFastBac HTa.PKBP146-467/PIF plasmid used subsequently used to generate a virus for production of the chimeric protein.

[0480] Generation of PKB (146-481)S474D Mutant.

[0481] This mutant was generated by Quikchange mutagenesis of the pFastBacHTa PKBβ (146-481) plasmid.

[0482] Template pFastBacHTa.PKBP146-481/2851a

[0483] Quikchange according to the manufacturers specifications using the following oligo's:

[0484] PKBPS474D upper: cac ttc ccc cag ttc GAC tac tcg gcc agc atc

[0485] PKBPS474D lower: gat gct ggc cga gta GTC gaa ctg ggg gaagtg

[0486] The reaction contained the following:

[0487] 5 μl 10×Pfu reaction buffer

[0488] 1 μl DNA template 40 ng

[0489] 41 μl ddH₂O

[0490] 1 μl upper strand oligonucleotide (30 picomoles)

[0491] 1 μl lower strand oligonucleotide (30 picomoles)

[0492] 1 μl Pfu (2.5 units from Stratagene)

[0493] The PCR cycling conditions were as follows:

[0494] 16 cycles of 30 sec. at 95° C., 60 sec. at 55° C. and 14 minutes at 68° C.

[0495] Following PCR the reaction was treated with 20 units of DpnI restriction enzyme for 4 hrs at 37° C. The treated DNA was used to transform XL-1 Blue (Stratagene) cells and bacteria were selected on ampicillin-agar plates. Plasmids DNA was prepared from transformed E. coli cultures using the Qiagen miniprep kit and sequenced on an Applied Biosystems 3700DNA analyzer.

[0496] Protein Expression and Purification

[0497] Expression of PKBβ-PIF

[0498] Generation of recombinant baculovirus using the GIBCO/Life Sciences Bacmid system was performed using standard procedures. Insect cells (density ˜2.0×10⁶ cells/ml, total volume of 2.7 L; 5.4×10⁹ Sf9 cells), grown in a culture of GIBCO/Life Sciences supplemented Sf900II medium were infected at a moiety of infection of 2 and grown for 72 hours prior to harvesting.

[0499] Purification of PKBβ-PIF

[0500] All procedures are performed at 4° C.

[0501] 1. Cell lysis: Insect cells are lysed in a Q-sepharose buffer A (25 mM Tris.HCl, [pH 7.5], 25 mM NaCl, 25 mM NaF, 25 mM β-glycerophosphate, 0.1% (v/v) P-mercaptoethanol, 2 mM benzamidine, 0.2 mM PMSF, 10% (v/v) glycerol, 1 μg/ml of DNAase, 2 μg/ml pepstatin, 2 μg/ml leupeptin, 2 μg/ml aprotinin A.

[0502] 2. Q-sepharose, anion exchange chromatography: The lysate is cleared by centrifugation and loaded onto a 50 mL Q-sepharose column equilibrated in buffer A. The column is washed in 300 mL of buffer A and PKB is eluted using 100 mL of buffer A+1 M NaCl.

[0503] 3. Ni-NTA affinity chromatography: The pH of the eluate is raised to 8.0 using a 1 M of Tris.HCl (pH 9.5) and this sample is loaded onto a Ni-NTA agarose column containing 10 mL of Ni-NTA agarose resin that had been pre-equilibrated in buffer B: 20 mM imidazole, 20 mM Tris.HCl (pH 8.0), 25 mM NaF, 25 mM β-glycerophosphate, 500 mM NaCl, 0.1% (v/v) β-mercaptoethanol, 2 mM benzamidine, 0.2 mM PMSF. The column is washed and the protein is eluted using a gradient to buffer B+300 mM imidazole. EDTA and DTT to final concentrations of 0.5 mM and 2 mM, respectively, are added immediately to the eluted protein.

[0504] 4. Tev protease cleavage. The 6×His affinity tag is removed by cleavage using Tev (tobacco etch virus) protease. Tev protease is added to PKB-PIF from step 3 (ratio of PKB-PIF:TEV of 15:1) and this solution is dialysed at 4° C. for 14 hr into buffer C: 50 mM Tris.HCl (pH 7.5), 150 mM NaCl, 5 mM DTT.

[0505] 5. Phosphorylation of PKB-PIF is carried out using PDK1purified in the inventors' laboratory. MgCl₂/ATP are added PKB from step 4 to a final concentration of 5 mM. PDK1 is added (ratio of PKB-PIF:PDK1of 8:1). The mixture is incubated at 20° C. for 2 to 3 hrs and then at 4° C. for 14 hrs. To prepare a stock solution of 50 mM ATP/Mg²+: Solid ATP is added to a solution of 50 mM MgCl₂ in 100 mM Tris.HCl (pH 9.5), 150, mM NaCl. ATP used is the magnesium salt: SIGMA catalogue code:A-9187. 9. To remove TEV and PDK1: Dialyse protein from step 5 into buffer B (from step 3) for 4 h at 4° C. in 4 L. This sample is loaded onto a Ni-NTA agarose column containing 10 mL of Ni-NTA agarose resin that had been pre-equilibrated in buffer B: 20 mM imidazole, 20 mM Tris.HCl (pH 8.0), 25 mM NaF, 25 mM β-glycerophosphate, 500 mM NaCl, 0.1% (v/v) β-mercaptoethanol, 2 mM benzamidine, 0.2 mM PMSF. PKB is collected in the flow through and first part of wash. EDTA and DTT to final concentrations of 0.5 mM and 2 mM, respectively, are added immediately to the eluted protein

[0506] 6. Phenyl TSK hydrophobic interaction chromatography: The protein from step 6 is brought to a concentration of ammonium sulphate in the range 1.5-1.7 M and loaded onto a phenyl TSK column equilibrated in buffer D: 50 mM Tris.HCl (pH 7.5), 1.5-1.7 M ammonium sulphate, 100 mM NaCl, 2 mM DTT, 0.5 mM EDTA, 2 mM benzamidine, 0.2 mM PMSF. The column is washed and PKB is eluted using a linear gradient developed to a buffer E consisting of 50 mM Tris.HCl (pH 7.5), 100 mM NaCl, 20% (v/v) glycerol, 2 mM DTT, 2 mM benzamidine, 0.5 mM EDTA, 0.2 mM PMSF.

[0507] 7. Mono-Q, anion exchange chromatography. The PKB-PIF collected in step 7 is dialysed into Mono-Q buffer F: 25 mM Tris.HCl (pH 7.5), 25 mM NaCl, 8% (v/v) glycerol, 0.5 mM EDTA, 2 mM DTT, 0.2 mM PMSF. The column is washed in the above buffer and the protein is eluted by developing a shallow gradient to buffer F+0.5 M NaCl.

[0508] 8. Size exclusion chromatography. The protein from step 8 is concentrated to <3 mL and loaded onto an S75 gel filtration column equilibrated in buffer G: 10 mM Tris.HCl (pH 7.5), 300 mM NaCl, 2 mM DTT.

[0509] Purification of PKB S474D

[0510] PKB S474D was purified as described above for PKB-PIF, except that:

[0511] 1. Phe-TSK column: 1.26 mM ammonium sulphate was used.

[0512] 2. Desalting was into MonoQ buffer F

[0513] 3. Protein concentration for crystallisation: 5 mg/ml, drop size: 3 ul+3 l.

[0514] Crystallisation of PKBβ-PIF

[0515] The protein from step 8 was concentrated to 10 mg/ml and AMPPNP/MnCl₂ was added (from a stock solution of 50 mM [see below]) to a final concentration of 5 mM. A 10-residue GSK-3 peptide (GRPRTTSFAE) was added to the protein solution to give a final concentration of 0.6 mM. Crystals were grown using the under-oil batch method. A small volume of protein/AMP-PNP/GSK-3 (1 μl) was mixed with an equal volume of crystallisation buffer: 22% (w/v) polyethylene glycol 4000, 10%-14% (v/v) isopropanol, 0.1 M Hepes (pH 7.5), 5 mM DTT, within individual wells of a 72 well polystyrene tray (Nunc) and immersed under 5 ml of silicone oil. The trays were incubated at 22° C. and crystals grow to a maximum size of 0.05 mm×0.05 mm×1.0 mm within 18 hours and exhibit a needle-like morphology. To prepare a stock solution of 50 mM AMP-PNP/Mn²⁺: Solid AMP-PNP is added to a solution of 50 mM MnCl₂ in 50 mM Tris.HCl (pH 7.5). AMP-PNP is lithium salt, SIGMA catalogue code: A-2647.

[0516] Data Collection and Structure Determination

[0517] Crystals were harvested from the crystallisation trays and incubated in a cryoprotection buffer consisting of 12% (w/v) polyethylene glycol 4000, 6% (v/v) isopropanol, 150 mM NaCl, 50 mM Tris.HCl (pH 7.5), 15% (v/v) methylpentane-diol, 0.5 mM AMPPNP/MnCl₂, 0.3 mM GSK3 peptide for 20 sees, prior to mounting the crystals in a ryan loop, and freezing in a nitrogen gas stream at 100 K X-ray diffraction data were collected at the European Synchrotron Radiation Facility, Grenoble, France.

[0518] Data were collected and these were analysed and processed using the CCP4 program suite (CCP4, 1994). The structure was solved by means of molecular replacement using the coordinates of the catalytic subunit of PKA as a search model with the program CNS (Brunger et al., 1998). The atomic structure was refined using rigid body and least squares refinement with CNS. Model building and analysis was done using O (Jones et al., 1991). Crystallographic data statistics are given in Table 2.

[0519] While the invention has been described in conjunction with the exemplary embodiments described above, many equivalent modifications and variations will be apparent to those skilled in the art when given this disclosure Accordingly, the exemplary embodiments of the invention set forth are considered to be illustrative and not limiting. Various changes to the described embodiments may be made without departing from the spirit and scope of the invention. The references in the above text and listed below are incorporated by reference insofar as is required for the skilled person to carry out the invention.

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TABLE 6 Coordinate data for PKB-PIF REMARK Written by O version 8.0.5 REMARK Wed Jul 10 19:14:27 2002 CRYST1 44.936 60.997 131.315 90.00 90.00 90.00 ORIGX1 1.000000 0.000000 0.000000 0.00000 ORIGX2 0.000000 1.000000 0.000000 0.00000 ORIGX3 0.000000 0.000000 1.000000 0.00000 SCALE1 0.022254 −0.000001   −0.000001   0.00000 SCALE2 0.000000 0.016394 0.000000 0.00000 SCALE3 0.000000 0.000000 0.007615 0.00000 ATOM 1 CB LYS A 146 35.598 46.504 91.726 1.00 38.99 6 ATOM 2 CG LYS A 146 35.641 44.989 91.480 1.00 39.59 6 ATOM 3 CD LYS A 146 35.546 44.679 89.995 1.00 41.03 6 ATOM 4 CE LYS A 146 35.890 43.223 89.697 1.00 41.18 6 ATOM 5 NZ LYS A 146 35.866 42.953 88.225 1.00 40.70 7 ATOM 6 C LYS A 146 37.330 46.656 93.551 1.00 37.52 6 ATOM 7 O LYS A 146 38.254 47.332 93.088 1.00 38.03 8 ATOM 8 N LYS A 146 35.572 48.396 93.337 1.00 37.08 7 ATOM 9 CA LYS A 146 35.875 46.945 93.172 1.00 37.17 6 ATOM 10 N VAL A 147 37.508 45.654 94.413 1.00 37.21 7 ATOM 11 CA VAL A 147 38.826 45.227 94.887 1.00 36.71 6 ATOM 12 CB VAL A 147 38.833 44.986 96.434 1.00 36.74 6 ATOM 13 CG1 VAL A 147 40.249 44.730 96.936 1.00 37.52 6 ATOM 14 CG2 VAL A 147 38.240 46.182 97.175 1.00 37.19 6 ATOM 15 C VAL A 147 39.202 43.941 94.143 1.00 36.20 6 ATOM 16 O VAL A 147 38.385 43.021 94.027 1.00 36.03 8 ATOM 17 N THR A 148 40.421 43.914 93.602 1.00 35.86 7 ATOM 18 CA THR A 148 40.932 42.764 92.851 1.00 35.62 6 ATOM 19 CB THR A 148 41.368 43.160 91.403 1.00 35.70 6 ATOM 20 OG1 THR A 148 42.327 44.225 91.454 1.00 36.61 8 ATOM 21 CG2 THR A 148 40.173 43.593 90.567 1.00 37.01 6 ATOM 22 C THR A 148 42.107 42.071 93.546 1.00 34.67 6 ATOM 23 O THR A 148 42.661 42.585 94.521 1.00 34.13 8 ATOM 24 N MET A 149 42.480 40.910 93.005 1.00 34.31 7 ATOM 25 CA MET A 149 43.579 40.073 93.495 1.00 33.74 6 ATOM 26 CB MET A 149 43.539 38.723 92.764 1.00 35.81 6 ATOM 27 CG MET A 149 44.114 37.542 93.525 1.00 37.55 6 ATOM 28 SD MET A 149 43.127 37.081 94.963 1.00 39.77 16 ATOM 29 CE MET A 149 42.247 35.720 94.311 1.00 39.13 6 ATOM 30 C MET A 149 44.938 40.751 93.265 1.00 33.47 6 ATOM 31 O MET A 149 45.853 40.620 94.084 1.00 31.64 8 ATOM 32 N ASN A 150 45.024 41.524 92.181 1.00 32.77 7 ATOM 33 CA ASN A 150 46.238 42.245 91.786 1.00 32.95 6 ATOM 34 CB ASN A 150 46.190 42.571 90.287 1.00 35.92 6 ATOM 35 CG ASN A 150 46.393 41.342 89.417 1.00 39.60 6 ATOM 36 OD1 ASN A 150 45.532 40.461 89.351 1.00 41.54 8 ATOM 37 ND2 ASN A 150 47.542 41.274 88.749 1.00 40.47 7 ATOM 38 C ASN A 150 46.569 43.508 92.590 1.00 31.47 6 ATOM 39 O ASN A 150 47.624 44.111 92.389 1.00 31.61 8 ATOM 40 N ASP A 151 45.681 43.890 93.510 1.00 29.83 7 ATOM 41 CA ASP A 151 45.886 45.067 94.363 1.00 28.23 6 ATOM 42 CB ASP A 151 44.540 45.598 94.888 1.00 30.09 6 ATOM 43 CG ASP A 151 43.627 46.119 93.782 1.00 32.08 6 ATOM 44 OD1 ASP A 151 44.130 46.648 92.765 1.00 34.40 8 ATOM 45 OD2 ASP A 151 42.392 46.008 93.941 1.00 33.26 8 ATOM 46 C ASP A 151 46.795 44.741 95.555 1.00 26.25 6 ATOM 47 O ASP A 151 47.169 45.633 96.325 1.00 25.26 8 ATOM 48 N PHE A 152 47.135 43.457 95.694 1.00 24.40 7 ATOM 49 CA PHE A 152 47.965 42.957 96.792 1.00 24.43 6 ATOM 50 CB PHE A 152 47.144 42.031 97.713 1.00 22.34 6 ATOM 51 CG PHE A 152 45.874 42.644 98.242 1.00 21.94 6 ATOM 52 CD1 PHE A 152 45.870 43.347 99.460 1.00 21.86 6 ATOM 53 CD2 PHE A 152 44.670 42.523 97.521 1.00 21.46 6 ATOM 54 CE1 PHE A 152 44.680 43.930 99.960 1.00 21.39 6 ATOM 55 CE2 PHE A 152 43.470 43.098 98.004 1.00 22.63 6 ATOM 56 CZ PHE A 152 43.473 43.805 99.227 1.00 21.83 6 ATOM 57 C PHE A 152 49.200 42.169 96.356 1.00 24.57 6 ATOM 58 O PHE A 152 49.237 41.595 95.267 1.00 24.79 8 ATOM 59 N GLU A 153 50.196 42.145 97.242 1.00 24.31 7 ATOM 60 CA GLU A 153 51.441 41.393 97.063 1.00 25.33 6 ATOM 61 CB GLU A 153 52.655 42.233 97.467 1.00 27.50 6 ATOM 62 CG GLU A 153 53.038 43.306 96.466 1.00 31.31 6 ATOM 63 CD GLU A 153 53.959 44.347 97.058 1.00 34.61 6 ATOM 64 OE1 GLU A 153 55.169 44.325 96.743 1.00 38.59 8 ATOM 65 OE2 CLU A 153 53.474 45.191 97.841 1.00 37.31 8 ATOM 66 C GLU A 153 51.297 40.212 98.019 1.00 25.65 6 ATOM 67 O GLU A 153 50.870 40.396 99.157 1.00 23.89 8 ATOM 68 N TYR A 154 51.616 39.010 97.543 1.00 25.47 7 ATOM 69 CA TYR A 154 51.501 37.782 98.336 1.00 25.80 6 ATOM 70 CB TYR A 154 50.809 36.687 97.505 1.00 25.23 6 ATOM 71 CG TYR A 154 49.421 37.102 97.066 1.00 24.77 6 ATOM 72 CD1 TYR A 154 49.233 37.912 95.921 1.00 23.17 6 ATOM 73 CE1 TYR A 154 47.954 38.439 95.593 1.00 23.31 6 ATOM 74 CD2 TYR A 154 48.296 36.808 97.863 1.00 23.33 6 ATOM 75 CE2 TYR A 154 47.013 37.327 97.545 1.00 22.63 6 ATOM 76 CZ TYR A 154 46.857 38.145 96.416 1.00 23.06 6 ATOM 77 OH TYR A 154 45.634 38.701 96.145 1.00 23.28 8 ATOM 78 C TYR A 154 52.874 37.356 98.838 1.00 26.25 6 ATOM 79 O TYR A 154 53.709 36.861 98.075 1.00 26.40 8 ATOM 80 N LEU A 155 53.087 37.565 100.138 1.00 26.02 7 ATOM 81 CA LEU A 155 54.365 37.289 100.794 1.00 26.19 6 ATOM 82 CB LEU A 155 54.622 38.343 101.875 1.00 25.69 6 ATOM 83 CG LEU A 155 54.463 39.802 101.418 1.00 27.24 6 ATOM 84 CD1 LEU A 155 54.496 40.706 102.609 1.00 29.07 6 ATOM 85 CD2 LEU A 155 55.529 40.201 100.397 1.00 28.00 6 ATOM 86 C LEU A 155 54.598 35.880 101.330 1.00 26.37 6 ATOM 87 O LEU A 155 55.494 35.184 100.844 1.00 28.06 8 ATOM 88 N LYS A 156 53.853 35.482 102.366 1.00 25.39 7 ATOM 89 CA LYS A 156 53.984 34.138 102.946 1.00 25.08 6 ATOM 90 CB LYS A 156 55.198 34.012 103.888 1.00 28.06 6 ATOM 91 CG LYS A 156 55.486 35.169 104.830 1.00 29.46 6 ATOM 92 CD LYS A 156 56.814 34.912 105.521 1.00 30.23 6 ATOM 93 CE LYS A 156 57.477 36.199 105.942 1.00 32.02 6 ATOM 94 NZ LYS A 156 58.713 35.963 106.735 1.00 31.98 7 ATOM 95 C LYS A 156 52.738 33.562 103.602 1.00 23.60 6 ATOM 96 O LYS A 156 51.844 34.298 104.027 1.00 23.61 8 ATOM 97 N LEU A 157 52.690 32.231 103.656 1.00 20.16 7 ATOM 98 CA LEU A 157 51.573 31.495 104.243 1.00 19.09 6 ATOM 99 CB LEU A 157 51.579 30.041 103.746 1.00 19.63 6 ATOM 100 CG LEU A 157 50.405 29.121 104.119 1.00 18.37 6 ATOM 101 CD1 LEU A 157 49.152 29.543 103.379 1.00 18.24 6 ATOM 102 CD2 LEU A 157 50.748 27.682 103.796 1.00 19.54 6 ATOM 103 C LEU A 157 51.618 31.536 105.772 1.00 19.08 6 ATOM 104 O LEU A 157 52.634 31.216 106.380 1.00 19.14 8 ATOM 105 N LEU A 158 50.509 31.962 106.373 1.00 17.83 7 ATOM 106 CA LEU A 158 50.387 32.054 107.827 1.00 16.37 6 ATOM 107 CB LEU A 158 49.565 33.286 108.207 1.00 14.71 6 ATOM 108 CG LEU A 158 50.110 34.646 107.780 1.00 14.55 6 ATOM 109 CD1 LEU A 158 49.076 35.708 108.064 1.00 14.27 6 ATOM 110 CD2 LEU A 158 51.426 34.948 108.490 1.00 15.52 6 ATOM 111 C LEU A 158 49.712 30.819 108.394 1.00 15.85 6 ATOM 112 O LEU A 158 50.089 30.329 109.461 1.00 16.43 8 ATOM 113 N GLY A 159 48.715 30.326 107.664 1.00 16.93 7 ATOM 114 CA GLY A 159 47.972 29.159 108.099 1.00 18.83 6 ATOM 115 C GLY A 159 47.282 28.456 106.956 1.00 20.79 6 ATOM 116 O GLY A 159 46.961 29.071 105.938 1.00 20.77 8 ATOM 117 N LYS A 160 47.039 27.162 107.142 1.00 24.18 7 ATOM 118 CA LYS A 160 46.397 26.334 106.131 1.00 28.23 6 ATOM 119 CB LYS A 160 47.464 25.606 105.297 1.00 29.69 6 ATOM 120 CG LYS A 160 46.957 24.862 104.065 1.00 31.54 6 ATOM 121 CD LYS A 160 48.108 24.198 103.329 1.00 34.23 6 ATOM 122 CE LYS A 160 47.622 23.454 102.098 1.00 36.48 6 ATOM 123 NZ LYS A 160 48.747 22.794 101.379 1.00 38.35 7 ATOM 124 C LYS A 160 45.467 25.327 106.793 1.00 31.17 6 ATOM 125 O LYS A 160 45.800 24.720 107.818 1.00 30.86 8 ATOM 126 N GLY A 161 44.290 25.185 106.196 1.00 33.09 7 ATOM 127 CA GLY A 161 43.297 24.249 106.675 1.00 36.29 6 ATOM 128 C GLY A 161 42.874 23.360 105.528 1.00 37.70 6 ATOM 129 O GLY A 161 43.416 23.453 104.420 1.00 38.10 8 ATOM 130 N THR A 162 41.877 22.520 105.788 1.00 39.10 7 ATOM 131 CA THR A 162 41.344 21.592 104.795 1.00 40.50 6 ATOM 132 CB THR A 162 40.517 20.466 105.478 1.00 41.35 6 ATOM 133 OG1 THR A 162 41.089 20.149 106.755 1.00 43.24 8 ATOM 134 CG2 THR A 162 40.518 19.206 104.628 1.00 41.85 6 ATOM 135 C THR A 162 40.446 22.338 103.798 1.00 40.35 6 ATOM 136 O THR A 162 40.287 21.907 102.656 1.00 41.36 8 ATOM 137 N PHE A 163 39.899 23.475 104.234 1.00 38.83 7 ATOM 138 CA PHE A 163 38.991 24.275 103.411 1.00 38.27 6 ATOM 139 CB PHE A 163 37.619 24.401 104.104 1.00 40.42 6 ATOM 140 CG PHE A 163 37.072 23.094 104.634 1.00 42.48 6 ATOM 141 CD1 PHE A 163 37.107 22.820 106.016 1.00 43.72 6 ATOM 142 CD2 PHE A 163 36.550 22.119 103.761 1.00 43.33 6 ATOM 143 CE1 PHE A 163 36.632 21.583 106.536 1.00 44.52 6 ATOM 144 CE2 PHE A 163 36.070 20.874 104.262 1.00 43.70 6 ATOM 145 CZ PHE A 163 36.112 20.606 105.653 1.00 44.30 6 ATOM 146 C PHE A 163 39.505 25.666 103.017 1.00 36.96 6 ATOM 147 O PHE A 163 38.818 26.385 102.283 1.00 38.92 8 ATOM 148 N GLY A 164 40.704 26.038 103.473 1.00 33.83 7 ATOM 149 CA GLY A 164 41.244 27.349 103.133 1.00 30.04 6 ATOM 150 C GLY A 164 42.664 27.679 103.553 1.00 27.55 6 ATOM 151 O GLY A 164 43.257 26.985 104.381 1.00 27.18 8 ATOM 152 N LYS A 165 43.206 28.742 102.949 1.00 24.49 7 ATOM 153 CA LYS A 165 44.567 29.231 103.211 1.00 22.73 6 ATOM 154 CB LYS A 165 45.433 29.142 101.939 1.00 25.16 6 ATOM 155 CG LYS A 165 45.642 27.740 101.370 1.00 28.79 6 ATOM 156 CD LYS A 165 46.406 27.765 100.047 1.00 30.63 6 ATOM 157 CE LYS A 165 47.892 27.494 100.245 1.00 33.30 6 ATOM 158 NZ LYS A 165 48.640 27.455 98.955 1.00 35.27 7 ATOM 159 C LYS A 165 44.540 30.694 103.666 1.00 20.60 6 ATOM 160 O LYS A 165 43.713 31.475 103.195 1.00 19.43 8 ATOM 161 N VAL A 166 45.422 31.043 104.605 1.00 17.73 7 ATOM 162 CA VAL A 166 45.548 32.415 105.114 1.00 15.78 6 ATOM 163 CB VAL A 166 45.286 32.521 106.651 1.00 14.50 6 ATOM 164 CG1 VAL A 166 45.447 33.971 107.133 1.00 15.35 6 ATOM 165 CG2 VAL A 166 43.884 32.041 106.979 1.00 15.62 6 ATOM 166 C VAL A 166 46.963 32.872 104.768 1.00 16.07 6 ATOM 167 O VAL A 166 47.943 32.277 105.215 1.00 15.08 8 ATOM 168 N ILE A 167 47.045 33.916 103.944 1.00 16.51 7 ATOM 169 CA ILE A 167 48.315 34.464 103.459 1.00 16.75 6 ATOM 170 CB ILE A 167 48.357 34.409 101.877 1.00 17.58 6 ATOM 171 CG2 ILE A 167 49.684 34.970 101.335 1.00 18.41 6 ATOM 172 CG1 ILE A 167 48.174 32.965 101.379 1.00 19.06 6 ATOM 173 CD1 ILE A 167 47.939 32.819 99.879 1.00 21.01 6 ATOM 174 C ILE A 167 48.556 35.909 103.922 1.00 15.18 6 ATOM 175 O ILE A 167 47.627 36.717 103.964 1.00 16.04 8 ATOM 176 N LEU A 168 49.813 36.219 104.252 1.00 15.97 7 ATOM 177 CA LEU A 168 50.218 37.569 104.655 1.00 16.22 6 ATOM 178 CB LEU A 168 51.566 37.559 105.395 1.00 16.65 6 ATOM 179 CG LEU A 168 52.219 38.895 105.791 1.00 16.16 6 ATOM 180 CD1 LEU A 168 51.300 39.745 106.657 1.00 15.72 6 ATOM 181 CD2 LEU A 168 53.524 38.624 106.501 1.00 16.81 6 ATOM 182 C LEU A 168 50.339 38.380 103.374 1.00 17.30 6 ATOM 183 O LEU A 168 51.116 38.031 102.480 1.00 17.71 8 ATOM 184 N VAL A 169 49.512 39.416 103.277 1.00 16.99 7 ATOM 185 CA VAL A 169 49.487 40.280 102.107 1.00 18.02 6 ATOM 186 CB VAL A 169 48.110 40.215 101.355 1.00 17.58 6 ATOM 187 CG1 VAL A 169 47.826 38.804 100.885 1.00 18.01 6 ATOM 188 CG2 VAL A 169 46.961 40.715 102.224 1.00 18.69 6 ATOM 189 C VAL A 169 49.836 41.728 102.422 1.00 19.08 6 ATOM 190 O VAL A 169 49.814 42.145 103.577 1.00 17.29 8 ATOM 191 N ARG A 170 50.199 42.470 101.379 1.00 20.20 7 ATOM 192 CA ARG A 170 50.529 43.884 101.498 1.00 22.10 6 ATOM 193 CB ARG A 170 52.032 44.122 101.273 1.00 24.17 6 ATOM 194 CG ARG A 170 52.477 45.558 101.549 1.00 28.32 6 ATOM 195 CD ARG A 170 53.946 45.799 101.240 1.00 31.96 6 ATOM 196 NE ARG A 170 54.347 47.135 101.685 1.00 36.98 7 ATOM 197 CZ ARG A 170 55.593 47.513 101.965 1.00 38.93 6 ATOM 198 NH1 ARG A 170 56.608 46.663 101.848 1.00 41.37 7 ATOM 199 NH2 ARG A 170 55.819 48.744 102.403 1.00 40.23 7 ATOM 200 C ARG A 170 49.727 44.608 100.427 1.00 22.53 6 ATOM 201 O ARG A 170 49.768 44.215 99.260 1.00 22.11 8 ATOM 202 N GLU A 171 48.967 45.630 100.827 1.00 22.10 7 ATOM 203 CA GLU A 171 48.189 46.417 99.871 1.00 22.97 6 ATOM 204 CB GLU A 171 47.071 47.205 100.561 1.00 24.48 6 ATOM 205 CG GLU A 171 46.025 47.758 99.579 1.00 25.87 6 ATOM 206 CD GLU A 171 44.955 48.619 100.233 1.00 28.74 6 ATOM 207 OE1 GLU A 171 44.597 48.373 101.405 1.00 30.01 8 ATOM 208 OE2 GLU A 171 44.458 49.548 99.562 1.00 31.24 8 ATOM 209 C GLU A 171 49.180 47.360 99.199 1.00 22.85 6 ATOM 210 O GLU A 171 49.881 48.114 99.875 1.00 23.04 8 ATOM 211 N LYS A 172 49.266 47.259 97.873 1.00 24.15 7 ATOM 212 CA LYS A 172 50.186 48.060 97.063 1.00 24.42 6 ATOM 213 CB LYS A 172 50.071 47.664 95.588 1.00 24.80 6 ATOM 214 CG LYS A 172 50.561 46.260 95.268 1.00 27.05 6 ATOM 215 CD LYS A 172 50.379 45.937 93.788 1.00 27.95 6 ATOM 216 CE LYS A 172 50.842 44.526 93.463 1.00 28.57 6 ATOM 217 NZ LYS A 172 50.564 44.152 92.045 1.00 29.36 7 ATOM 218 C LYS A 172 50.049 49.576 97.203 1.00 24.45 6 ATOM 219 O LYS A 172 51.050 50.275 97.362 1.00 24.35 8 ATOM 220 N ALA A 173 48.805 50.053 97.239 1.00 24.81 7 ATOM 221 CA ALA A 173 48.492 51.480 97.337 1.00 24.93 6 ATOM 222 CB ALA A 173 47.045 51.720 96.922 1.00 26.20 6 ATOM 223 C ALA A 173 48.767 52.155 98.678 1.00 25.88 6 ATOM 224 O ALA A 173 49.084 53.349 98.719 1.00 25.43 8 ATOM 225 N THR A 174 48.653 51.391 99.764 1.00 25.17 7 ATOM 226 CA THR A 174 48.853 51.923 101.113 1.00 24.98 6 ATOM 227 CB THR A 174 47.645 51.600 102.022 1.00 25.77 6 ATOM 228 OG1 THR A 174 47.469 50.180 102.096 1.00 26.13 8 ATOM 229 CG2 THR A 174 46.364 52.242 101.492 1.00 26.33 6 ATOM 230 C THR A 174 50.122 51.450 101.821 1.00 24.30 6 ATOM 231 O THR A 174 50.628 52.134 102.716 1.00 24.18 8 ATOM 232 N GLY A 175 50.613 50.272 101.434 1.00 23.34 7 ATOM 233 CA GLY A 175 51.803 49.701 102.049 1.00 23.13 6 ATOM 234 C GLY A 175 51.485 48.985 103.354 1.00 23.48 6 ATOM 235 O GLY A 175 52.392 48.510 104.044 1.00 22.03 8 ATOM 236 N ARG A 176 50.192 48.914 103.682 1.00 24.06 7 ATOM 237 CA ARG A 176 49.700 48.268 104.902 1.00 23.49 6 ATOM 238 CB ARG A 176 48.367 48.886 105.341 1.00 26.59 6 ATOM 239 CG ARG A 176 48.487 50.325 105.824 1.00 30.97 6 ATOM 240 CD ARG A 176 47.136 50.918 106.180 1.00 35.94 6 ATOM 241 NE ARG A 176 47.235 52.350 106.462 1.00 41.42 7 ATOM 242 CZ ARG A 176 46.257 53.100 106.969 1.00 43.79 6 ATOM 243 NH1 ARG A 176 45.075 52.569 107.269 1.00 45.62 7 ATOM 244 NH2 ARG A 176 46.461 54.395 107.172 1.00 44.85 7 ATOM 245 C ARG A 176 49.569 46.756 104.752 1.00 22.48 6 ATOM 246 O ARG A 176 49.192 46.252 103.689 1.00 20.68 8 ATOM 247 N TYR A 177 49.882 46.047 105.834 1.00 19.60 7 ATOM 248 CA TYR A 177 49.848 44.589 105.862 1.00 20.49 6 ATOM 249 CB TYR A 177 51.059 44.046 106.621 1.00 20.40 6 ATOM 250 CG TYR A 177 52.386 44.338 105.956 1.00 22.09 6 ATOM 251 CD1 TYR A 177 52.962 45.628 106.008 1.00 22.39 6 ATOM 252 CE1 TYR A 177 54.228 45.895 105.418 1.00 24.16 6 ATOM 253 CD2 TYR A 177 53.099 43.318 105.297 1.00 23.49 6 ATOM 254 CE2 TYR A 177 54.365 43.575 104.706 1.00 25.39 6 ATOM 255 CZ TYR A 177 54.918 44.859 104.773 1.00 25.11 6 ATOM 256 OH TYR A 177 56.144 45.094 104.198 1.00 27.13 8 ATOM 257 C TYR A 177 48.564 44.025 106.442 1.00 18.10 6 ATOM 258 O TYR A 177 48.010 44.569 107.400 1.00 19.84 8 ATOM 259 N TYR A 178 48.066 42.969 105.799 1.00 16.41 7 ATOM 260 CA TYR A 178 46.831 42.290 106.190 1.00 15.68 6 ATOM 261 CB TYR A 178 45.665 42.743 105.294 1.00 16.76 6 ATOM 262 CG TYR A 178 45.330 44.217 105.346 1.00 18.56 6 ATOM 263 CD1 TYR A 178 45.679 45.076 104.279 1.00 18.90 6 ATOM 264 CE1 TYR A 178 45.401 46.470 104.339 1.00 19.66 6 ATOM 265 CD2 TYR A 178 44.692 44.774 106.474 1.00 18.88 6 ATOM 266 CE2 TYR A 178 44.411 46.163 106.548 1.00 20.27 6 ATOM 267 CZ TYR A 178 44.770 47.000 105.477 1.00 21.34 6 ATOM 268 OH TYR A 178 44.501 48.343 105.553 1.00 22.68 8 ATOM 269 C TYR A 178 46.971 40.773 106.056 1.00 15.15 6 ATOM 270 O TYR A 178 47.951 40.273 105.504 1.00 16.38 8 ATOM 271 N ALA A 179 45.998 40.048 106.601 1.00 14.45 7 ATOM 272 CA ALA A 179 45.963 38.593 106.497 1.00 15.00 6 ATOM 273 CB ALA A 179 45.789 37.960 107.864 1.00 15.67 6 ATOM 274 C ALA A 179 44.771 38.276 105.601 1.00 16.10 6 ATOM 275 O ALA A 179 43.641 38.670 105.904 1.00 16.60 8 ATOM 276 N MET A 180 45.033 37.629 104.466 1.00 15.47 7 ATOM 277 CA MET A 180 43.965 37.287 103.534 1.00 15.01 6 ATOM 278 CB MET A 180 44.334 37.676 102.096 1.00 16.40 6 ATOM 279 CG MET A 180 43.153 37.649 101.127 1.00 17.98 6 ATOM 280 SD MET A 180 43.635 37.674 99.390 1.00 20.77 16 ATOM 281 CE MET A 180 44.059 39.348 99.202 1.00 17.71 6 ATOM 282 C MET A 180 43.592 35.813 103.584 1.00 14.04 6 ATOM 283 O MET A 180 44.426 34.952 103.318 1.00 14.85 8 ATOM 284 N LYS A 181 42.332 35.540 103.930 1.00 15.56 7 ATOM 285 CA LYS A 181 41.815 34.176 103.983 1.00 15.94 6 ATOM 286 CB LYS A 181 40.787 34.014 105.109 1.00 16.20 6 ATOM 287 CG LYS A 181 40.264 32.592 105.300 1.00 15.27 6 ATOM 288 CD LYS A 181 39.372 32.503 106.522 1.00 15.79 6 ATOM 289 CE LYS A 181 38.863 31.086 106.731 1.00 15.36 6 ATOM 290 NZ LYS A 181 38.114 30.981 108.017 1.00 16.70 7 ATOM 291 C LYS A 181 41.181 33.906 102.622 1.00 17.88 6 ATOM 292 O LYS A 181 40.260 34.615 102.202 1.00 16.98 8 ATOM 293 N ILE A 182 41.731 32.915 101.924 1.00 18.70 7 ATOM 294 CA ILE A 182 41.278 32.533 100.590 1.00 20.08 6 ATOM 295 CB ILE A 182 42.472 32.504 99.577 1.00 20.31 6 ATOM 296 CG2 ILE A 182 41.979 32.124 98.174 1.00 21.67 6 ATOM 297 CG1 ILE A 182 43.157 33.878 99.526 1.00 21.09 6 ATOM 298 CD1 ILE A 182 44.441 33.936 98.718 1.00 23.19 6 ATOM 299 C ILE A 182 40.573 31.177 100.622 1.00 19.76 6 ATOM 300 O ILE A 182 41.124 30.183 101.104 1.00 19.95 8 ATOM 301 N LEU A 183 39.337 31.168 100.127 1.00 20.47 7 ATOM 302 CA LEU A 183 38.511 29.964 100.061 1.00 21.62 6 ATOM 303 CB LEU A 183 37.239 30.136 100.905 1.00 23.22 6 ATOM 304 CG LEU A 183 37.265 30.456 102.408 1.00 24.40 6 ATOM 305 CD1 LEU A 183 35.858 30.412 102.953 1.00 25.40 6 ATOM 306 CD2 LEU A 183 38.120 29.475 103.171 1.00 27.44 6 ATOM 307 C LEU A 183 38.132 29.701 98.604 1.00 22.11 6 ATOM 308 O LEU A 183 37.911 30.640 97.842 1.00 21.49 8 ATOM 309 N ARG A 184 38.076 28.427 98.222 1.00 23.42 7 ATOM 310 CA ARG A 184 37.724 28.033 96.852 1.00 24.98 6 ATOM 311 CB ARG A 184 38.509 26.787 96.434 1.00 26.20 6 ATOM 312 CG ARG A 184 40.015 26.978 96.420 1.00 30.11 6 ATOM 313 CD ARG A 184 40.730 25.710 96.006 1.00 33.19 6 ATOM 314 NE ARG A 184 42.181 25.885 96.027 1.00 37.08 7 ATOM 315 CZ ARG A 184 43.003 25.545 95.036 1.00 37.18 6 ATOM 316 NH1 ARG A 184 42.531 24.999 93.920 1.00 37.82 7 ATOM 317 NH2 ARG A 184 44.306 25.753 95.162 1.00 39.05 7 ATOM 318 C ARG A 184 36.224 27.778 96.727 1.00 25.20 6 ATOM 319 O ARG A 184 35.671 26.944 97.449 1.00 25.19 8 ATOM 320 N LYS A 185 35.581 28.486 95.795 1.00 26.11 7 ATOM 321 CA LYS A 185 34.134 28.379 95.553 1.00 27.69 6 ATOM 322 CB LYS A 185 33.693 29.316 94.425 1.00 28.30 6 ATOM 323 CG LYS A 185 33.676 30.779 94.790 1.00 28.29 6 ATOM 324 CD LYS A 185 33.089 31.611 93.666 1.00 29.31 6 ATOM 325 CE LYS A 185 33.089 33.084 94.023 1.00 30.13 6 ATOM 326 NZ LYS A 185 32.434 33.920 92.983 1.00 30.44 7 ATOM 327 C LYS A 185 33.609 26.979 95.255 1.00 28.46 6 ATOM 328 O LYS A 185 32.593 26.581 95.817 1.00 28.57 8 ATOM 329 N GLU A 186 34.336 26.229 94.423 1.00 29.72 7 ATOM 330 CA GLU A 186 33.957 24.868 94.028 1.00 30.93 6 ATOM 331 CB GLU A 186 34.898 24.352 92.929 1.00 33.98 6 ATOM 332 CG GLU A 186 34.364 23.142 92.151 1.00 38.41 6 ATOM 333 CD GLU A 186 35.256 22.739 90.994 1.00 40.85 6 ATOM 334 OE1 GLU A 186 36.267 22.043 91.232 1.00 42.60 8 ATOM 335 OE2 GLU A 186 34.938 23.112 89.844 1.00 43.56 8 ATOM 336 C GLU A 186 33.893 23.871 95.195 1.00 30.07 6 ATOM 337 O GLU A 186 32.998 23.026 95.236 1.00 29.75 8 ATOM 338 N VAL A 187 34.805 24.023 96.158 1.00 29.33 7 ATOM 339 CA VAL A 187 34.881 23.162 97.349 1.00 28.73 6 ATOM 340 CB VAL A 187 36.247 23.358 98.092 1.00 28.62 6 ATOM 341 CG1 VAL A 187 36.376 22.426 99.300 1.00 28.38 6 ATOM 342 CG2 VAL A 187 37.401 23.106 97.137 1.00 29.33 6 ATOM 343 C VAL A 187 33.714 23.458 98.307 1.00 29.11 6 ATOM 344 O VAL A 187 33.129 22.543 98.891 1.00 28.94 8 ATOM 345 N ILE A 188 33.365 24.739 98.412 1.00 29.71 7 ATOM 346 CA ILE A 188 32.286 25.224 99.275 1.00 30.27 6 ATOM 347 CB ILE A 188 32.399 26.767 99.436 1.00 29.90 6 ATOM 348 CG2 ILE A 188 31.207 27.354 100.182 1.00 28.87 6 ATOM 349 CG1 ILE A 188 33.682 27.096 100.198 1.00 30.65 6 ATOM 350 CD1 ILE A 188 34.051 28.532 100.147 1.00 31.52 6 ATOM 351 C ILE A 188 30.893 24.806 98.782 1.00 31.15 6 ATOM 352 O ILE A 188 30.064 24.354 99.580 1.00 30.84 8 ATOM 353 N ILE A 189 30.665 24.933 97.473 1.00 32.14 7 ATOM 354 CA ILE A 189 29.389 24.575 96.836 1.00 33.04 6 ATOM 355 CB ILE A 189 29.320 25.119 95.363 1.00 33.40 6 ATOM 356 CG2 ILE A 189 28.000 24.714 94.672 1.00 33.20 6 ATOM 357 CG1 ILE A 189 29.417 26.651 95.370 1.00 32.93 6 ATOM 358 CD1 ILE A 189 29.841 27.263 94.041 1.00 32.11 6 ATOM 359 C ILE A 189 29.154 23.056 96.875 1.00 33.24 6 ATOM 360 O ILE A 189 28.045 22.608 97.179 1.00 33.53 8 ATOM 361 N ALA A 190 30.221 22.286 96.640 1.00 33.49 7 ATOM 362 CA ALA A 190 30.174 20.819 96.635 1.00 33.51 6 ATOM 363 CB ALA A 190 31.478 20.254 96.085 1.00 33.97 6 ATOM 364 C ALA A 190 29.877 20.210 98.007 1.00 34.08 6 ATOM 365 O ALA A 190 29.206 19.181 98.103 1.00 33.95 8 ATOM 366 N LYS A 191 30.366 20.867 99.058 1.00 35.22 7 ATOM 367 CA LYS A 191 30.163 20.413 100.434 1.00 35.85 6 ATOM 368 CB LYS A 191 31.459 20.572 101.237 1.00 37.79 6 ATOM 369 CG LYS A 191 32.534 19.584 100.803 1.00 41.20 6 ATOM 370 CD LYS A 191 33.896 19.929 101.356 1.00 43.63 6 ATOM 371 CE LYS A 191 34.953 18.978 100.813 1.00 45.49 6 ATOM 372 NZ LYS A 191 36.319 19.306 101.307 1.00 46.74 7 ATOM 373 C LYS A 191 28.981 21.091 101.130 1.00 35.21 6 ATOM 374 O LYS A 191 28.750 20.875 102.324 1.00 34.90 8 ATOM 375 N ASP A 192 28.223 21.876 100.352 1.00 34.34 7 ATOM 376 CA ASP A 192 27.022 22.618 100.784 1.00 34.64 6 ATOM 377 CB ASP A 192 25.847 21.640 101.013 1.00 36.56 6 ATOM 378 CG ASP A 192 24.488 22.275 100.752 1.00 38.94 6 ATOM 379 OD1 ASP A 192 23.760 22.544 101.729 1.00 41.27 8 ATOM 380 OD2 ASP A 192 24.149 22.498 99.569 1.00 41.23 8 ATOM 381 C ASP A 192 27.261 23.529 102.005 1.00 33.71 6 ATOM 382 O ASP A 192 26.474 23.552 102.959 1.00 34.09 8 ATOM 383 N GLU A 193 28.365 24.275 101.951 1.00 31.63 7 ATOM 384 CA GLU A 193 28.766 25.179 103.028 1.00 30.31 6 ATOM 385 CB GLU A 193 30.192 24.837 103.492 1.00 30.38 6 ATOM 386 CG GLU A 193 30.330 23.520 104.262 1.00 30.72 6 ATOM 387 CD GLU A 193 29.593 23.522 105.594 1.00 31.98 6 ATOM 388 OE1 GLU A 193 29.907 24.374 106.452 1.00 32.63 8 ATOM 389 OE2 GLU A 193 28.700 22.669 105.783 1.00 32.37 8 ATOM 390 C GLU A 193 28.661 26.671 102.693 1.00 29.34 6 ATOM 391 O GLU A 193 29.343 27.499 103.310 1.00 29.54 8 ATOM 392 N VAL A 194 27.788 27.010 101.741 1.00 26.95 7 ATOM 393 CA VAL A 194 27.573 28.397 101.303 1.00 26.02 6 ATOM 394 CB VAL A 194 26.683 28.457 100.014 1.00 26.60 6 ATOM 395 CG1 VAL A 194 26.412 29.905 99.583 1.00 26.04 6 ATOM 396 CG2 VAL A 194 27.367 27.711 98.875 1.00 26.87 6 ATOM 397 C VAL A 194 26.992 29.279 102.415 1.00 24.83 6 ATOM 398 O VAL A 194 27.488 30.384 102.643 1.00 23.94 8 ATOM 399 N ALA A 195 26.004 28.750 103.141 1.00 24.47 7 ATOM 400 CA ALA A 195 25.339 29.463 104.238 1.00 23.92 6 ATOM 401 CB ALA A 195 24.219 28.608 104.822 1.00 24.42 6 ATOM 402 C ALA A 195 26.307 29.894 105.342 1.00 23.16 6 ATOM 403 O ALA A 195 26.259 31.036 105.797 1.00 23.24 8 ATOM 404 N HIS A 196 27.232 29.001 105.696 1.00 22.24 7 ATOM 405 CA HIS A 196 28.235 29.265 106.728 1.00 21.09 6 ATOM 406 CB HIS A 196 28.910 27.962 107.175 1.00 21.72 6 ATOM 407 CG HIS A 196 28.052 27.098 108.051 1.00 22.17 6 ATOM 408 CD2 HIS A 196 27.028 27.400 108.885 1.00 23.83 6 ATOM 409 ND1 HIS A 196 28.220 25.733 108.133 1.00 23.27 7 ATOM 410 CE1 HIS A 196 27.337 25.232 108.978 1.00 23.89 6 ATOM 411 NE2 HIS A 196 26.601 26.222 109.448 1.00 23.92 7 ATOM 412 C HIS A 196 29.291 30.279 106.294 1.00 20.95 6 ATOM 413 O HIS A 196 29.738 31.095 107.103 1.00 20.73 8 ATOM 414 N THR A 197 29.638 30.250 105.005 1.00 20.34 7 ATOM 415 CA THR A 197 30.631 31.158 104.422 1.00 20.27 6 ATOM 416 CB THR A 197 31.092 30.659 103.032 1.00 21.83 6 ATOM 417 OG1 THR A 197 31.473 29.281 103.127 1.00 22.29 8 ATOM 418 CG2 THR A 197 32.294 31.453 102.546 1.00 23.08 6 ATOM 419 C THR A 197 30.087 32.589 104.316 1.00 19.65 6 ATOM 420 O THR A 197 30.822 33.552 104.546 1.00 19.14 8 ATOM 421 N VAL A 198 28.796 32.711 103.996 1.00 20.24 7 ATOM 422 CA VAL A 198 28.127 34.012 103.885 1.00 20.52 6 ATOM 423 CB VAL A 198 26.745 33.888 103.153 1.00 22.07 6 ATOM 424 CG1 VAL A 198 26.004 35.231 103.120 1.00 24.56 6 ATOM 425 CG2 VAL A 198 26.961 33.415 101.723 1.00 24.03 6 ATOM 426 C VAL A 198 27.972 34.615 105.290 1.00 19.88 6 ATOM 427 O VAL A 198 28.184 35.816 105.475 1.00 18.95 8 ATOM 428 N THR A 199 27.689 33.756 106.275 1.00 20.08 7 ATOM 429 CA THR A 199 27.538 34.165 107.676 1.00 19.65 6 ATOM 430 CB THR A 199 26.976 33.012 108.556 1.00 20.55 6 ATOM 431 OG1 THR A 199 25.710 32.593 108.033 1.00 24.39 8 ATOM 432 CG2 THR A 199 26.769 33.455 110.006 1.00 22.78 6 ATOM 433 C THR A 199 28.890 34.646 108.216 1.00 18.06 6 ATOM 434 O THR A 199 28.941 35.624 108.955 1.00 18.63 8 ATOM 435 N GLU A 200 29.978 34.004 107.775 1.00 17.08 7 ATOM 436 CA GLU A 200 31.340 34.375 108.185 1.00 17.20 6 ATOM 437 CB GLU A 200 32.372 33.409 107.589 1.00 17.18 6 ATOM 438 CG GLU A 200 33.831 33.711 107.975 1.00 17.75 6 ATOM 439 CD GLU A 200 34.819 32.627 107.568 1.00 18.91 6 ATOM 440 OE1 GLU A 200 34.429 31.648 106.889 1.00 19.30 8 ATOM 441 OE2 GLU A 200 35.997 32.751 107.955 1.00 18.68 8 ATOM 442 C GLU A 200 31.636 35.806 107.736 1.00 17.74 6 ATOM 443 O GLU A 200 32.164 36.605 108.509 1.00 17.90 8 ATOM 444 N SER A 201 31.230 36.131 106.507 1.00 17.42 7 ATOM 445 CA SER A 201 31.420 37.469 105.956 1.00 19.19 6 ATOM 446 CB SER A 201 31.127 37.488 104.458 1.00 20.04 6 ATOM 447 OG SER A 201 31.464 38.745 103.893 1.00 24.22 8 ATOM 448 C SER A 201 30.535 38.481 106.672 1.00 18.03 6 ATOM 449 O SER A 201 31.025 39.520 107.091 1.00 19.22 8 ATOM 450 N ARG A 202 29.265 38.123 106.885 1.00 18.72 7 ATOM 451 CA ARG A 202 28.285 38.985 107.562 1.00 19.77 6 ATOM 452 CB ARG A 202 26.901 38.336 107.566 1.00 21.33 6 ATOM 453 CG ARG A 202 26.153 38.409 106.244 1.00 25.41 6 ATOM 454 CD ARG A 202 24.773 37.749 106.349 1.00 28.21 6 ATOM 455 NE ARG A 202 23.947 38.331 107.412 1.00 32.27 7 ATOM 456 CZ ARG A 202 23.174 39.410 107.282 1.00 34.81 6 ATOM 457 NH1 ARG A 202 22.475 39.847 108.322 1.00 36.21 7 ATOM 458 NH2 ARG A 202 23.088 40.051 106.121 1.00 35.27 7 ATOM 459 C ARG A 202 28.674 39.354 108.994 1.00 19.14 6 ATOM 460 O ARG A 202 28.530 40.510 109.396 1.00 18.54 8 ATOM 461 N VAL A 203 29.213 38.380 109.733 1.00 18.46 7 ATOM 462 CA VAL A 203 29.650 38.595 111.115 1.00 18.50 6 ATOM 463 CB VAL A 203 29.955 37.247 111.848 1.00 17.92 6 ATOM 464 CG1 VAL A 203 30.570 37.487 113.228 1.00 17.80 6 ATOM 465 CG2 VAL A 203 28.667 36.466 112.027 1.00 17.41 6 ATOM 466 C VAL A 203 30.860 39.529 111.123 1.00 19.29 6 ATOM 467 O VAL A 203 30.896 40.478 111.899 1.00 20.87 8 ATOM 468 N LEU A 204 31.794 39.306 110.198 1.00 18.77 7 ATOM 469 CA LEU A 204 32.993 40.137 110.070 1.00 19.46 6 ATOM 470 CB LEU A 204 33.972 39.500 109.084 1.00 18.79 6 ATOM 471 CG LEU A 204 34.971 38.473 109.618 1.00 18.35 6 ATOM 472 CD1 LEU A 204 35.506 37.622 108.483 1.00 18.91 6 ATOM 473 CD2 LEU A 204 36.106 39.176 110.364 1.00 19.88 6 ATOM 474 C LEU A 204 32.658 41.572 109.634 1.00 21.48 6 ATOM 475 O LEU A 204 33.339 42.517 110.030 1.00 23.72 8 ATOM 476 N GLN A 205 31.573 41.722 108.870 1.00 21.94 7 ATOM 477 CA GLN A 205 31.111 43.028 108.386 1.00 22.75 6 ATOM 478 CB GLN A 205 30.117 42.862 107.233 1.00 23.21 6 ATOM 479 CG GLN A 205 30.682 42.303 105.954 1.00 22.92 6 ATOM 480 CD GLN A 205 29.624 42.116 104.881 1.00 23.61 6 ATOM 481 OE1 GLN A 205 28.788 42.989 104.657 1.00 24.78 8 ATOM 482 NE2 GLN A 205 29.667 40.976 104.203 1.00 23.68 7 ATOM 483 C GLN A 205 30.399 43.836 109.463 1.00 23.71 6 ATOM 484 O GLN A 205 30.567 45.056 109.548 1.00 26.35 8 ATOM 485 N ASN A 206 29.599 43.141 110.272 1.00 23.54 7 ATOM 486 CA ASN A 206 28.791 43.768 111.314 1.00 22.93 6 ATOM 487 CB ASN A 206 27.356 43.228 111.241 1.00 25.18 6 ATOM 488 CG ASN A 206 26.659 43.597 109.938 1.00 27.49 6 ATOM 489 OD1 ASN A 206 26.158 44.713 109.782 1.00 29.50 8 ATOM 490 ND2 ASN A 206 26.650 42.668 108.988 1.00 27.87 7 ATOM 491 C ASN A 206 29.308 43.751 112.753 1.00 22.84 6 ATOM 492 O ASN A 206 28.541 44.009 113.690 1.00 23.66 8 ATOM 493 N THR A 207 30.590 43.434 112.936 1.00 19.60 7 ATOM 494 CA THR A 207 31.188 43.431 114.276 1.00 18.32 6 ATOM 495 CB THR A 207 31.697 42.034 114.723 1.00 17.82 6 ATOM 496 OG1 THR A 207 32.561 41.476 113.724 1.00 16.82 8 ATOM 497 CG2 THR A 207 30.534 41.097 115.015 1.00 17.66 6 ATOM 498 C THR A 207 32.329 44.428 114.406 1.00 17.60 6 ATOM 499 O THR A 207 33.115 44.617 113.475 1.00 18.46 8 ATOM 500 N ARG A 208 32.391 45.072 115.569 1.00 18.08 7 ATOM 501 CA ARG A 208 33.423 46.055 115.883 1.00 19.07 6 ATOM 502 CB ARG A 208 32.955 47.472 115.492 1.00 22.44 6 ATOM 503 CG ARG A 208 34.007 48.319 114.759 1.00 28.18 6 ATOM 504 CD ARG A 208 34.291 47.822 113.334 1.00 29.41 6 ATOM 505 NE ARG A 208 33.486 48.497 112.311 1.00 31.02 7 ATOM 506 CZ ARG A 208 32.813 47.884 111.336 1.00 31.40 6 ATOM 507 NH1 ARG A 208 32.818 46.559 111.226 1.00 29.96 7 ATOM 508 NH2 ARG A 208 32.151 48.607 110.440 1.00 32.21 7 ATOM 509 C ARG A 208 33.710 45.956 117.383 1.00 17.63 6 ATOM 510 O ARG A 208 32.905 46.383 118.214 1.00 18.31 8 ATOM 511 N HIS A 209 34.841 45.337 117.716 1.00 15.81 7 ATOM 512 CA HIS A 209 35.258 45.142 119.107 1.00 15.05 6 ATOM 513 CB HIS A 209 34.624 43.847 119.657 1.00 15.47 6 ATOM 514 CG HIS A 209 34.799 43.641 121.132 1.00 15.16 6 ATOM 515 CD2 HIS A 209 35.762 42.999 121.833 1.00 13.71 6 ATOM 516 ND1 HIS A 209 33.919 44.145 122.065 1.00 17.11 7 ATOM 517 CE1 HIS A 209 34.337 43.826 123.277 1.00 12.83 6 ATOM 518 NE2 HIS A 209 35.454 43.131 123.164 1.00 17.36 7 ATOM 519 C HIS A 209 36.787 45.044 119.132 1.00 15.22 6 ATOM 520 O HIS A 209 37.382 44.474 118.212 1.00 14.48 8 ATOM 521 N PRO A 210 37.445 45.591 120.184 1.00 14.91 7 ATOM 522 CD PRO A 210 36.962 46.482 121.258 1.00 16.37 6 ATOM 523 CA PRO A 210 38.911 45.512 120.241 1.00 14.27 6 ATOM 524 CB PRO A 210 39.249 46.304 121.513 1.00 15.83 6 ATOM 525 CG PRO A 210 37.996 46.263 122.313 1.00 18.36 6 ATOM 526 C PRO A 210 39.537 44.111 120.259 1.00 12.15 6 ATOM 527 O PRO A 210 40.696 43.955 119.882 1.00 13.33 8 ATOM 528 N PHE A 211 38.770 43.095 120.665 1.00 11.27 7 ATOM 529 CA PHE A 211 39.299 41.732 120.726 1.00 9.95 6 ATOM 530 CB PHE A 211 39.135 41.142 122.141 1.00 10.98 6 ATOM 531 CG PHE A 211 39.670 42.042 123.229 1.00 9.84 6 ATOM 532 CD1 PHE A 211 40.959 42.608 123.124 1.00 12.37 6 ATOM 533 CD2 PHE A 211 38.852 42.414 124.308 1.00 13.84 6 ATOM 534 CE1 PHE A 211 41.421 43.543 124.072 1.00 11.66 6 ATOM 535 CE2 PHE A 211 39.304 43.350 125.273 1.00 13.03 6 ATOM 536 CZ PHE A 211 40.591 43.916 125.149 1.00 12.92 6 ATOM 537 C PHE A 211 38.802 40.786 119.645 1.00 11.10 6 ATOM 538 O PHE A 211 38.948 39.566 119.753 1.00 11.16 8 ATOM 539 N LEU A 212 38.212 41.369 118.604 1.00 11.06 7 ATOM 540 CA LEU A 212 37.738 40.617 117.448 1.00 11.91 6 ATOM 541 CB LEU A 212 36.233 40.815 117.204 1.00 12.23 6 ATOM 542 CG LEU A 212 35.191 40.292 118.199 1.00 11.56 6 ATOM 543 CD1 LEU A 212 33.827 40.576 117.641 1.00 12.46 6 ATOM 544 CD2 LEU A 212 35.333 38.813 118.470 1.00 10.73 6 ATOM 545 C LEU A 212 38.502 41.150 116.249 1.00 12.30 6 ATOM 546 O LEU A 212 38.702 42.366 116.122 1.00 13.20 8 ATOM 547 N THR A 213 38.974 40.235 115.403 1.00 11.37 7 ATOM 548 CA THR A 213 39.689 40.586 114.176 1.00 12.19 6 ATOM 549 CB THR A 213 40.194 39.313 113.448 1.00 13.41 6 ATOM 550 OG1 THR A 213 41.133 38.632 114.284 1.00 13.30 8 ATOM 551 CG2 THR A 213 40.874 39.649 112.136 1.00 13.02 6 ATOM 552 C THR A 213 38.706 41.343 113.279 1.00 12.71 6 ATOM 553 O THR A 213 37.580 40.888 113.064 1.00 14.89 8 ATOM 554 N ALA A 214 39.120 42.527 112.831 1.00 13.30 7 ATOM 555 CA ALA A 214 38.283 43.360 111.975 1.00 14.74 6 ATOM 556 CB ALA A 214 38.477 44.821 112.315 1.00 16.15 6 ATOM 557 C ALA A 214 38.558 43.107 110.498 1.00 14.13 6 ATOM 558 O ALA A 214 39.677 42.739 110.116 1.00 15.15 8 ATOM 559 N LEU A 215 37.514 43.276 109.687 1.00 14.65 7 ATOM 560 CA LEU A 215 37.582 43.070 108.242 1.00 15.66 6 ATOM 561 CB LEU A 215 36.303 42.375 107.753 1.00 17.50 6 ATOM 562 CG LEU A 215 36.224 41.855 106.309 1.00 18.01 6 ATOM 563 CD1 LEU A 215 37.090 40.625 106.141 1.00 17.63 6 ATOM 564 CD2 LEU A 215 34.788 41.519 105.962 1.00 17.61 6 ATOM 565 C LEU A 215 37.765 44.389 107.494 1.00 16.79 6 ATOM 566 O LEU A 215 37.013 45.346 107.706 1.00 16.84 8 ATOM 567 N LYS A 216 38.772 44.425 106.624 1.00 15.92 7 ATOM 568 CA LYS A 216 39.059 45.604 105.812 1.00 17.88 6 ATOM 569 CB LYS A 216 40.568 45.729 105.564 1.00 18.11 6 ATOM 570 CG LYS A 216 41.015 46.979 104.799 1.00 20.25 6 ATOM 571 CD LYS A 216 40.861 48.277 105.576 1.00 23.74 6 ATOM 572 CE LYS A 216 41.327 49.458 104.734 1.00 23.61 6 ATOM 573 NZ LYS A 216 41.289 50.736 105.492 1.00 27.06 7 ATOM 574 C LYS A 216 38.277 45.484 104.500 1.00 19.41 6 ATOM 575 O LYS A 216 37.499 46.375 104.155 1.00 20.52 8 ATOM 576 N TYR A 217 38.501 44.393 103.767 1.00 20.33 7 ATOM 577 CA TYR A 217 37.795 44.151 102.504 1.00 21.54 6 ATOM 578 CB TYR A 217 38.678 44.403 101.263 1.00 22.41 6 ATOM 579 CG TYR A 217 39.470 45.689 101.205 1.00 23.42 6 ATOM 580 CD1 TYR A 217 38.831 46.946 101.119 1.00 24.90 6 ATOM 581 CE1 TYR A 217 39.587 48.147 101.033 1.00 25.62 6 ATOM 582 CD2 TYR A 217 40.878 45.654 101.203 1.00 24.52 6 ATOM 583 CE2 TYR A 217 41.645 46.844 101.114 1.00 25.18 6 ATOM 584 CZ TYR A 217 40.991 48.082 101.032 1.00 25.16 6 ATOM 585 OH TYR A 217 41.733 49.235 100.966 1.00 26.08 8 ATOM 586 C TYR A 217 37.335 42.705 102.420 1.00 21.74 6 ATOM 587 O TYR A 217 37.902 41.815 103.052 1.00 20.96 8 ATOM 588 N ALA A 218 36.304 42.490 101.613 1.00 22.24 7 ATOM 589 CA ALA A 218 35.759 41.168 101.344 1.00 23.85 6 ATOM 590 CB ALA A 218 34.527 40.890 102.192 1.00 25.66 6 ATOM 591 C ALA A 218 35.397 41.238 99.869 1.00 25.38 6 ATOM 592 O ALA A 218 34.610 42.096 99.462 1.00 26.61 8 ATOM 593 N PHE A 219 36.077 40.427 99.060 1.00 25.93 7 ATOM 594 CA PHE A 219 35.831 40.396 97.622 1.00 26.13 6 ATOM 595 CB PHE A 219 36.823 41.311 96.857 1.00 26.71 6 ATOM 596 CG PHE A 219 38.264 40.833 96.857 1.00 27.75 6 ATOM 597 CD1 PHE A 219 39.115 41.108 97.946 1.00 27.52 6 ATOM 598 CD2 PHE A 219 38.791 40.144 95.741 1.00 27.78 6 ATOM 599 CE1 PHE A 219 40.482 40.704 97.925 1.00 28.24 6 ATOM 600 CE2 PHE A 219 40.149 39.732 95.705 1.00 28.11 6 ATOM 601 CZ PHE A 219 41.000 40.014 96.801 1.00 27.67 6 ATOM 602 C PHE A 219 35.837 38.983 97.065 1.00 26.63 6 ATOM 603 O PHE A 219 36.222 38.032 97.750 1.00 26.35 8 ATOM 604 N GLN A 220 35.445 38.865 95.799 1.00 27.67 7 ATOM 605 CA GLN A 220 35.406 37.577 95.127 1.00 29.16 6 ATOM 606 CB GLN A 220 34.012 36.940 95.248 1.00 29.39 6 ATOM 607 CG GLN A 220 32.849 37.765 94.701 1.00 30.69 6 ATOM 608 CD GLN A 220 31.507 37.132 94.993 1.00 30.68 6 ATOM 609 OE1 GLN A 220 31.180 36.067 94.466 1.00 31.49 8 ATOM 610 NE2 GLN A 220 30.722 37.778 95.847 1.00 30.59 7 ATOM 611 C GLN A 220 35.830 37.652 93.670 1.00 30.49 6 ATOM 612 O GLN A 220 35.779 38.717 93.045 1.00 30.46 8 ATOM 613 N THR A 221 36.330 36.522 93.176 1.00 31.94 7 ATOM 614 CA THR A 221 36.753 36.367 91.786 1.00 34.30 6 ATOM 615 CB THR A 221 38.241 35.921 91.670 1.00 33.98 6 ATOM 616 OG1 THR A 221 38.436 34.687 92.371 1.00 33.81 8 ATOM 617 CG2 THR A 221 39.179 36.986 92.229 1.00 34.65 6 ATOM 618 C THR A 221 35.820 35.306 91.190 1.00 35.99 6 ATOM 619 O THR A 221 34.765 35.020 91.766 1.00 36.47 8 ATOM 620 N HIS A 222 36.211 34.710 90.063 1.00 37.93 7 ATOM 621 CA HIS A 222 35.403 33.685 89.398 1.00 39.37 6 ATOM 622 CB HIS A 222 35.832 33.540 87.933 1.00 42.24 6 ATOM 623 CG HIS A 222 35.609 34.774 87.113 1.00 45.27 6 ATOM 624 CD2 HIS A 222 36.475 35.560 86.431 1.00 46.04 6 ATOM 625 ND1 HIS A 222 34.362 35.336 86.936 1.00 46.16 7 ATOM 626 CE1 HIS A 222 34.470 36.415 86.180 1.00 46.67 6 ATOM 627 NE2 HIS A 222 35.742 36.573 85.860 1.00 46.66 7 ATOM 628 C HIS A 222 35.436 32.322 90.096 1.00 39.06 6 ATOM 629 O HIS A 222 34.485 31.543 89.981 1.00 40.15 8 ATOM 630 N ASP A 223 36.500 32.069 90.861 1.00 37.82 7 ATOM 631 CA ASP A 223 36.665 30.798 91.569 1.00 36.30 6 ATOM 632 CB ASP A 223 37.636 29.878 90.794 1.00 38.54 6 ATOM 633 CG ASP A 223 39.044 30.474 90.625 1.00 40.31 6 ATOM 634 OD1 ASP A 223 39.217 31.711 90.708 1.00 42.05 8 ATOM 635 OD2 ASP A 223 39.986 29.685 90.395 1.00 41.81 8 ATOM 636 C ASP A 223 37.080 30.888 93.044 1.00 34.41 6 ATOM 637 O ASP A 223 37.150 29.863 93.728 1.00 32.93 8 ATOM 638 N ARG A 224 37.344 32.102 93.532 1.00 32.31 7 ATOM 639 CA ARG A 224 37.777 32.303 94.921 1.00 30.75 6 ATOM 640 CB ARG A 224 39.278 32.644 94.961 1.00 33.00 6 ATOM 641 CG ARG A 224 40.210 31.454 94.722 1.00 35.74 6 ATOM 642 CD ARG A 224 41.614 31.896 94.360 1.00 40.62 6 ATOM 643 NE ARG A 224 42.535 30.765 94.242 1.00 43.58 7 ATOM 644 CZ ARG A 224 43.847 30.871 94.040 1.00 44.59 6 ATOM 645 NH1 ARG A 224 44.423 32.063 93.928 1.00 44.53 7 ATOM 646 NH2 ARG A 224 44.591 29.775 93.955 1.00 45.52 7 ATOM 647 C ARG A 224 36.994 33.339 95.730 1.00 28.53 6 ATOM 648 O ARG A 224 36.375 34.246 95.173 1.00 27.31 8 ATOM 649 N LEU A 225 36.999 33.150 97.053 1.00 26.16 7 ATOM 650 CA LEU A 225 36.349 34.040 98.021 1.00 22.96 6 ATOM 651 CB LEU A 225 35.297 33.285 98.842 1.00 23.83 6 ATOM 652 CG LEU A 225 33.989 32.881 98.159 1.00 23.24 6 ATOM 653 CD1 LEU A 225 33.245 31.926 99.030 1.00 24.99 6 ATOM 654 CD2 LEU A 225 33.126 34.085 97.840 1.00 23.77 6 ATOM 655 C LEU A 225 37.461 34.534 98.937 1.00 21.31 6 ATOM 656 O LEU A 225 38.182 33.723 99.525 1.00 20.59 8 ATOM 657 N CYS A 226 37.597 35.853 99.061 1.00 20.16 7 ATOM 658 CA CYS A 226 38.666 36.435 99.874 1.00 19.26 6 ATOM 659 CB CYS A 226 39.666 37.152 98.968 1.00 20.69 6 ATOM 660 SG CYS A 226 40.223 36.209 97.529 1.00 23.93 16 ATOM 661 C CYS A 226 38.255 37.384 100.995 1.00 18.47 6 ATOM 662 O CYS A 226 37.469 38.309 100.785 1.00 18.75 8 ATOM 663 N PHE A 227 38.822 37.151 102.179 1.00 17.78 7 ATOM 664 CA PHE A 227 38.584 37.980 103.366 1.00 16.65 6 ATOM 665 CB PHE A 227 38.223 37.134 104.596 1.00 18.11 6 ATOM 666 CG PHE A 227 37.031 36.249 104.429 1.00 19.38 6 ATOM 667 CD1 PHE A 227 37.188 34.923 103.988 1.00 22.41 6 ATOM 668 CD2 PHE A 227 35.757 36.690 104.815 1.00 21.36 6 ATOM 669 CE1 PHE A 227 36.090 34.034 103.942 1.00 22.75 6 ATOM 670 CE2 PHE A 227 34.646 35.812 104.777 1.00 21.47 6 ATOM 671 CZ PHE A 227 34.814 34.478 104.341 1.00 21.05 6 ATOM 672 C PHE A 227 39.905 38.672 103.695 1.00 16.35 6 ATOM 673 O PHE A 227 40.874 38.000 104.040 1.00 17.04 8 ATOM 674 N VAL A 228 39.947 39.999 103.593 1.00 14.84 7 ATOM 675 CA VAL A 228 41.158 40.765 103.911 1.00 15.40 6 ATOM 676 CB VAL A 228 41.390 41.911 102.884 1.00 15.78 6 ATOM 677 CG1 VAL A 228 42.698 42.615 103.133 1.00 16.04 6 ATOM 678 CG2 VAL A 228 41.377 41.357 101.469 1.00 17.87 6 ATOM 679 C VAL A 228 40.947 41.292 105.335 1.00 15.23 6 ATOM 680 O VAL A 228 40.203 42.246 105.558 1.00 15.67 8 ATOM 681 N MET A 229 41.566 40.596 106.286 1.00 16.37 7 ATOM 682 CA MET A 229 41.459 40.888 107.720 1.00 17.24 6 ATOM 683 CB MET A 229 41.332 39.573 108.489 1.00 18.32 6 ATOM 684 CG MET A 229 40.269 38.609 108.026 1.00 21.23 6 ATOM 685 SD MET A 229 40.494 37.062 108.916 1.00 22.76 16 ATOM 686 CE MET A 229 41.840 36.338 107.997 1.00 22.29 6 ATOM 687 C MET A 229 42.689 41.587 108.275 1.00 16.70 6 ATOM 688 O MET A 229 43.761 41.523 107.672 1.00 16.74 8 ATOM 689 N GLU A 230 42.556 42.178 109.469 1.00 16.42 7 ATOM 690 CA GLU A 230 43.704 42.817 110.108 1.00 16.70 6 ATOM 691 CB GLU A 230 43.300 43.786 111.236 1.00 22.16 6 ATOM 692 CG GLU A 230 42.577 43.199 112.433 1.00 25.42 6 ATOM 693 CD GLU A 230 42.077 44.249 113.428 1.00 25.88 6 ATOM 694 OE1 GLU A 230 42.543 45.414 113.419 1.00 26.11 8 ATOM 695 OE2 GLU A 230 41.196 43.897 114.232 1.00 24.20 8 ATOM 696 C GLU A 230 44.635 41.692 110.578 1.00 15.64 6 ATOM 697 O GLU A 230 44.178 40.625 111.018 1.00 14.93 8 ATOM 698 N TYR A 231 45.920 41.888 110.316 1.00 13.70 7 ATOM 699 CA TYR A 231 46.961 40.920 110.636 1.00 13.55 6 ATOM 700 CB TYR A 231 48.192 41.204 109.753 1.00 13.44 6 ATOM 701 CG TYR A 231 49.441 40.374 110.005 1.00 14.19 6 ATOM 702 CD1 TYR A 231 49.386 38.966 110.117 1.00 14.55 6 ATOM 703 CE1 TYR A 231 50.559 38.203 110.361 1.00 15.67 6 ATOM 704 CD2 TYR A 231 50.698 41.003 110.134 1.00 15.11 6 ATOM 705 CE2 TYR A 231 51.879 40.247 110.370 1.00 16.61 6 ATOM 706 CZ TYR A 231 51.797 38.853 110.485 1.00 17.48 6 ATOM 707 OH TYR A 231 52.929 38.119 110.747 1.00 18.78 8 ATOM 708 C TYR A 231 47.334 40.892 112.114 1.00 12.31 6 ATOM 709 O TYR A 231 47.705 41.911 112.695 1.00 14.17 8 ATOM 710 N ALA A 232 47.234 39.699 112.695 1.00 12.54 7 ATOM 711 CA ALA A 232 47.589 39.482 114.091 1.00 11.51 6 ATOM 712 CB ALA A 232 46.648 38.477 114.714 1.00 12.28 6 ATOM 713 C ALA A 232 49.040 38.991 114.119 1.00 11.28 6 ATOM 714 O ALA A 232 49.313 37.794 113.990 1.00 12.06 8 ATOM 715 N ASN A 233 49.960 39.952 114.262 1.00 11.06 7 ATOM 716 CA ASN A 233 51.418 39.733 114.278 1.00 13.60 6 ATOM 717 CB ASN A 233 52.162 41.058 114.515 1.00 16.45 6 ATOM 718 CG ASN A 233 51.891 42.096 113.450 1.00 20.27 6 ATOM 719 OD1 ASN A 233 52.758 42.394 112.626 1.00 21.96 8 ATOM 720 ND2 ASN A 233 50.692 42.666 113.466 1.00 19.96 7 ATOM 721 C ASN A 233 51.942 38.742 115.308 1.00 13.84 6 ATOM 722 O ASN A 233 52.962 38.085 115.080 1.00 14.15 8 ATOM 723 N GLY A 234 51.229 38.641 116.429 1.00 11.74 7 ATOM 724 CA GLY A 234 51.638 37.770 117.515 1.00 11.57 6 ATOM 725 C GLY A 234 51.371 36.286 117.424 1.00 12.20 6 ATOM 726 O GLY A 234 51.730 35.561 118.343 1.00 12.22 8 ATOM 727 N GLY A 235 50.747 35.834 116.338 1.00 10.42 7 ATOM 728 CA GLY A 235 50.468 34.414 116.168 1.00 12.47 6 ATOM 729 C GLY A 235 49.352 33.866 117.035 1.00 10.95 6 ATOM 730 O GLY A 235 48.650 34.623 117.705 1.00 11.78 8 ATOM 731 N GLU A 236 49.177 32.546 116.987 1.00 10.95 7 ATOM 732 CA GLU A 236 48.144 31.852 117.758 1.00 10.49 6 ATOM 733 CB GLU A 236 47.929 30.440 117.221 1.00 12.70 6 ATOM 734 CG GLU A 236 47.556 30.319 115.772 1.00 13.27 6 ATOM 735 CD GLU A 236 47.608 28.880 115.273 1.00 13.93 6 ATOM 736 OE1 GLU A 236 48.174 28.004 115.964 1.00 15.46 8 ATOM 737 OE2 GLU A 236 47.070 28.623 114.182 1.00 14.90 8 ATOM 738 C GLU A 236 48.536 31.693 119.213 1.00 12.34 6 ATOM 739 O GLU A 236 49.717 31.561 119.531 1.00 10.74 8 ATOM 740 N LEU A 237 47.527 31.596 120.078 1.00 11.55 7 ATOM 741 CA LEU A 237 47.740 31.367 121.506 1.00 13.29 6 ATOM 742 CB LEU A 237 46.419 31.508 122.270 1.00 14.42 6 ATOM 743 CG LEU A 237 46.438 32.016 123.714 1.00 18.60 6 ATOM 744 CD1 LEU A 237 47.166 33.356 123.818 1.00 16.35 6 ATOM 745 CD2 LEU A 237 45.005 32.156 124.205 1.00 16.85 6 ATOM 746 C LEU A 237 48.293 29.942 121.629 1.00 12.92 6 ATOM 747 O LEU A 237 49.074 29.649 122.532 1.00 14.01 8 ATOM 748 N PHE A 238 47.965 29.113 120.628 1.00 11.90 7 ATOM 749 CA PHE A 238 48.419 27.724 120.518 1.00 13.50 6 ATOM 750 CB PHE A 238 47.749 27.047 119.304 1.00 14.41 6 ATOM 751 CG PHE A 238 48.067 25.572 119.145 1.00 16.03 6 ATOM 752 CD1 PHE A 238 47.996 24.678 120.240 1.00 18.08 6 ATOM 753 CD2 PHE A 238 48.453 25.070 117.887 1.00 17.79 6 ATOM 754 CE1 PHE A 238 48.312 23.304 120.079 1.00 17.35 6 ATOM 755 CE2 PHE A 238 48.768 23.696 117.712 1.00 18.93 6 ATOM 756 CZ PHE A 238 48.698 22.812 118.812 1.00 17.35 6 ATOM 757 C PHE A 238 49.941 27.669 120.389 1.00 12.66 6 ATOM 758 O PHE A 238 50.573 26.827 121.015 1.00 12.96 8 ATOM 759 N PHE A 239 50.516 28.597 119.620 1.00 12.53 7 ATOM 760 CA PHE A 239 51.970 28.666 119.422 1.00 12.41 6 ATOM 761 CB PHE A 239 52.313 29.767 118.394 1.00 12.06 6 ATOM 762 CG PHE A 239 53.768 29.796 117.977 1.00 13.71 6 ATOM 763 CD1 PHE A 239 54.208 29.031 116.880 1.00 14.81 6 ATOM 764 CD2 PHE A 239 54.715 30.559 118.698 1.00 13.77 6 ATOM 765 CE1 PHE A 239 55.577 29.016 116.503 1.00 16.72 6 ATOM 766 CE2 PHE A 239 56.090 30.554 118.337 1.00 15.61 6 ATOM 767 CZ PHE A 239 56.521 29.780 117.237 1.00 17.17 6 ATOM 768 C PHE A 239 52.700 28.941 120.743 1.00 11.84 6 ATOM 769 O PHE A 239 53.676 28.261 121.070 1.00 13.11 8 ATOM 770 N HIS A 240 52.211 29.942 121.476 1.00 11.72 7 ATOM 771 CA HIS A 240 52.790 30.372 122.747 1.00 11.29 6 ATOM 772 CB HIS A 240 52.210 31.722 123.156 1.00 11.11 6 ATOM 773 CG HIS A 240 52.460 32.796 122.149 1.00 11.01 6 ATOM 774 CD2 HIS A 240 51.638 33.376 121.245 1.00 12.50 6 ATOM 775 ND1 HIS A 240 53.712 33.325 121.927 1.00 12.86 7 ATOM 776 CE1 HIS A 240 53.649 34.180 120.923 1.00 13.24 6 ATOM 777 NE2 HIS A 240 52.402 34.228 120.491 1.00 12.17 7 ATOM 778 C HIS A 240 52.635 29.369 123.867 1.00 12.95 6 ATOM 779 O HIS A 240 53.583 29.128 124.616 1.00 13.88 8 ATOM 780 N LEU A 241 51.454 28.756 123.948 1.00 12.02 7 ATOM 781 CA LEU A 241 51.183 27.758 124.972 1.00 12.51 6 ATOM 782 CB LEU A 241 49.681 27.489 125.098 1.00 11.91 6 ATOM 783 CG LEU A 241 49.248 26.637 126.296 1.00 12.53 6 ATOM 784 CD1 LEU A 241 49.621 27.298 127.609 1.00 13.03 6 ATOM 785 CD2 LEU A 241 47.783 26.412 126.227 1.00 12.41 6 ATOM 786 C LEU A 241 51.950 26.466 124.716 1.00 13.13 6 ATOM 787 O LEU A 241 52.417 25.843 125.661 1.00 13.58 8 ATOM 788 N SER A 242 52.119 26.099 123.445 1.00 14.03 7 ATOM 789 CA SER A 242 52.868 24.889 123.084 1.00 15.82 6 ATOM 790 CB SER A 242 52.749 24.585 121.592 1.00 15.04 6 ATOM 791 OG SER A 242 51.418 24.242 121.252 1.00 19.04 8 ATOM 792 C SER A 242 54.341 25.040 123.459 1.00 16.86 6 ATOM 793 O SER A 242 54.952 24.096 123.957 1.00 18.49 8 ATOM 794 N ARG A 243 54.867 26.255 123.292 1.00 15.48 7 ATOM 795 CA ARG A 243 56.257 26.581 123.612 1.00 16.34 6 ATOM 796 CB ARG A 243 56.642 27.922 122.955 1.00 16.88 6 ATOM 797 CG ARG A 243 58.095 28.390 123.168 1.00 18.93 6 ATOM 798 CD ARG A 243 58.294 29.850 122.748 1.00 19.47 6 ATOM 799 NE ARG A 243 57.538 30.788 123.585 1.00 22.91 7 ATOM 800 CZ ARG A 243 56.671 31.696 123.131 1.00 23.62 6 ATOM 801 NH1 ARG A 243 56.425 31.817 121.833 1.00 23.76 7 ATOM 802 NH2 ARG A 243 56.025 32.473 123.987 1.00 24.68 7 ATOM 803 C ARG A 243 56.494 26.647 125.126 1.00 15.26 6 ATOM 804 O ARG A 243 57.421 26.014 125.640 1.00 16.98 8 ATOM 805 N GLU A 244 55.620 27.371 125.826 1.00 14.28 7 ATOM 806 CA GLU A 244 55.724 27.572 127.271 1.00 14.52 6 ATOM 807 CB GLU A 244 55.109 28.921 127.652 1.00 17.01 6 ATOM 808 CG GLU A 244 55.886 30.116 127.104 1.00 21.11 6 ATOM 809 CD GLU A 244 55.344 31.453 127.574 1.00 24.36 6 ATOM 810 OE1 GLU A 244 54.926 31.564 128.747 1.00 27.60 8 ATOM 811 OE2 GLU A 244 55.354 32.409 126.772 1.00 27.59 8 ATOM 812 C GLU A 244 55.150 26.471 128.158 1.00 12.96 6 ATOM 813 O GLU A 244 55.410 26.458 129.365 1.00 13.38 8 ATOM 814 N ARG A 245 54.434 25.525 127.534 1.00 13.94 7 ATOM 815 CA ARG A 245 53.763 24.360 128.163 1.00 14.01 6 ATOM 816 CB ARG A 245 54.706 23.493 129.036 1.00 16.24 6 ATOM 817 CG ARG A 245 56.060 23.080 128.436 1.00 20.52 6 ATOM 818 CD ARG A 245 55.966 22.358 127.107 1.00 21.96 6 ATOM 819 NE ARG A 245 57.286 21.861 126.717 1.00 22.92 7 ATOM 820 CZ ARG A 245 57.900 22.123 125.566 1.00 21.92 6 ATOM 821 NH1 ARG A 245 57.332 22.894 124.647 1.00 21.67 7 ATOM 822 NH2 ARG A 245 59.081 21.575 125.321 1.00 21.94 7 ATOM 823 C ARG A 245 52.531 24.740 128.987 1.00 14.87 6 ATOM 824 O ARG A 245 51.468 24.127 128.848 1.00 14.16 8 ATOM 825 N VAL A 246 52.686 25.768 129.819 1.00 13.22 7 ATOM 826 CA VAL A 246 51.634 26.246 130.709 1.00 13.49 6 ATOM 827 CB VAL A 246 51.646 25.409 132.045 1.00 13.87 6 ATOM 828 CG1 VAL A 246 52.913 25.677 132.872 1.00 17.88 6 ATOM 829 CG2 VAL A 246 50.385 25.630 132.849 1.00 14.92 6 ATOM 830 C VAL A 246 51.817 27.747 130.985 1.00 12.49 6 ATOM 831 O VAL A 246 52.928 28.272 130.882 1.00 14.56 8 ATOM 832 N PHE A 247 50.709 28.435 131.268 1.00 12.15 7 ATOM 833 CA PHE A 247 50.734 29.856 131.603 1.00 10.96 6 ATOM 834 CB PHE A 247 49.621 30.638 130.878 1.00 9.30 6 ATOM 835 CG PHE A 247 49.815 30.808 129.384 1.00 10.75 6 ATOM 836 CD1 PHE A 247 51.080 30.681 128.770 1.00 11.59 6 ATOM 837 CD2 PHE A 247 48.707 31.134 128.583 1.00 10.23 6 ATOM 838 CE1 PHE A 247 51.233 30.880 127.369 1.00 13.01 6 ATOM 839 CE2 PHE A 247 48.837 31.335 127.186 1.00 10.25 6 ATOM 840 CZ PHE A 247 50.108 31.209 126.574 1.00 11.78 6 ATOM 841 C PHE A 247 50.438 29.956 133.089 1.00 11.65 6 ATOM 842 O PHE A 247 49.819 29.055 133.669 1.00 13.93 8 ATOM 843 N THR A 248 50.841 31.072 133.697 1.00 12.27 7 ATOM 844 CA THR A 248 50.547 31.327 135.110 1.00 12.37 6 ATOM 845 CB THR A 248 51.325 32.557 135.648 1.00 14.86 6 ATOM 846 OG1 THR A 248 50.939 33.729 134.918 1.00 14.64 8 ATOM 847 CG2 THR A 248 52.830 32.350 135.517 1.00 15.18 6 ATOM 848 C THR A 248 49.046 31.651 135.159 1.00 13.21 6 ATOM 849 O THR A 248 48.446 31.979 134.124 1.00 12.83 8 ATOM 850 N GLU A 249 48.445 31.566 136.343 1.00 12.56 7 ATOM 851 CA GLU A 249 47.022 31.864 136.496 1.00 13.61 6 ATOM 852 CB GLU A 249 46.545 31.518 137.898 1.00 13.49 6 ATOM 853 CG GLU A 249 46.509 30.020 138.155 1.00 15.22 6 ATOM 854 CD GLU A 249 45.811 29.660 139.442 1.00 16.83 6 ATOM 855 OE1 GLU A 249 44.944 30.441 139.896 1.00 18.71 8 ATOM 856 OE2 GLU A 249 46.114 28.581 139.995 1.00 16.06 8 ATOM 857 C GLU A 249 46.685 33.313 136.164 1.00 12.75 6 ATOM 858 O GLU A 249 45.629 33.581 135.594 1.00 12.67 8 ATOM 859 N GLU A 250 47.636 34.215 136.426 1.00 12.45 7 ATOM 860 CA GLU A 250 47.467 35.641 136.152 1.00 13.29 6 ATOM 861 CB GLU A 250 48.533 36.469 136.886 1.00 17.16 6 ATOM 862 CG GLU A 250 48.223 37.970 137.002 1.00 22.23 6 ATOM 863 CD GLU A 250 47.034 38.270 137.911 1.00 24.68 6 ATOM 864 OE1 GLU A 250 47.184 38.164 139.147 1.00 31.36 8 ATOM 865 OE2 GLU A 250 45.953 38.615 137.393 1.00 26.06 8 ATOM 866 C GLU A 250 47.508 35.918 134.646 1.00 11.94 6 ATOM 867 O GLU A 250 46.737 36.739 134.144 1.00 13.21 8 ATOM 868 N ARG A 251 48.364 35.189 133.928 1.00 11.70 7 ATOM 869 CA ARG A 251 48.482 35.342 132.476 1.00 12.38 6 ATOM 870 CB ARG A 251 49.755 34.666 131.949 1.00 13.12 6 ATOM 871 CG ARG A 251 49.908 34.762 130.444 1.00 15.27 6 ATOM 872 CD ARG A 251 51.325 34.733 129.970 1.00 17.39 6 ATOM 873 NE ARG A 251 51.365 34.932 128.524 1.00 17.47 7 ATOM 874 CZ ARG A 251 52.292 34.426 127.717 1.00 17.60 6 ATOM 875 NH1 ARG A 251 53.274 33.690 128.209 1.00 21.21 7 ATOM 876 NH2 ARG A 251 52.213 34.625 126.410 1.00 18.01 7 ATOM 877 C ARG A 251 47.236 34.780 131.788 1.00 11.76 6 ATOM 878 O ARG A 251 46.707 35.395 130.856 1.00 12.20 8 ATOM 879 N ALA A 252 46.746 33.649 132.297 1.00 11.06 7 ATOM 880 CA ALA A 252 45.543 33.006 131.769 1.00 10.45 6 ATOM 881 CB ALA A 252 45.372 31.652 132.374 1.00 11.17 6 ATOM 882 C ALA A 252 44.316 33.868 132.055 1.00 10.89 6 ATOM 883 O ALA A 252 43.399 33.939 131.235 1.00 11.64 8 ATOM 884 N ARG A 253 44.339 34.562 133.197 1.00 10.82 7 ATOM 885 CA ARG A 253 43.249 35.460 133.589 1.00 10.50 6 ATOM 886 CB ARG A 253 43.446 35.960 135.023 1.00 11.20 6 ATOM 887 CG ARG A 253 42.408 36.983 135.525 1.00 12.57 6 ATOM 888 CD ARG A 253 42.253 36.983 137.046 1.00 17.07 6 ATOM 889 NE ARG A 253 43.523 36.861 137.753 1.00 20.66 7 ATOM 890 CZ ARG A 253 43.815 35.901 138.629 1.00 18.82 6 ATOM 891 NH1 ARG A 253 42.926 34.964 138.939 1.00 17.58 7 ATOM 892 NH2 ARG A 253 45.037 35.830 139.125 1.00 19.03 7 ATOM 893 C ARG A 253 43.160 36.637 132.624 1.00 10.05 6 ATOM 894 O ARG A 253 42.063 37.023 132.240 1.00 9.54 8 ATOM 895 N PHE A 254 44.316 37.171 132.217 1.00 10.68 7 ATOM 896 CA PHE A 254 44.365 38.294 131.276 1.00 10.56 6 ATOM 897 CB PHE A 254 45.813 38.759 131.037 1.00 11.01 6 ATOM 898 CG PHE A 254 45.930 39.938 130.091 1.00 12.84 6 ATOM 899 CD1 PHE A 254 45.866 41.253 130.583 1.00 15.95 6 ATOM 900 CD2 PHE A 254 46.081 39.738 128.694 1.00 14.78 6 ATOM 901 CE1 PHE A 254 45.945 42.363 129.701 1.00 17.52 6 ATOM 902 CE2 PHE A 254 46.162 40.834 127.800 1.00 15.81 6 ATOM 903 CZ PHE A 254 46.091 42.153 128.310 1.00 16.73 6 ATOM 904 C PHE A 254 43.708 37.910 129.947 1.00 9.27 6 ATOM 905 O PHE A 254 42.827 38.623 129.465 1.00 9.85 8 ATOM 906 N TYR A 255 44.147 36.791 129.367 1.00 8.55 7 ATOM 907 CA TYR A 255 43.605 36.311 128.094 1.00 8.18 6 ATOM 908 CB TYR A 255 44.416 35.127 127.553 1.00 8.20 6 ATOM 909 CG TYR A 255 45.846 35.466 127.182 1.00 9.18 6 ATOM 910 CD1 TYR A 255 46.173 36.690 126.554 1.00 9.54 6 ATOM 911 CE1 TYR A 255 47.519 37.024 126.246 1.00 9.52 6 ATOM 912 CD2 TYR A 255 46.892 34.578 127.487 1.00 9.66 6 ATOM 913 CE2 TYR A 255 48.240 34.899 127.177 1.00 10.46 6 ATOM 914 CZ TYR A 255 48.541 36.120 126.561 1.00 10.83 6 ATOM 915 OH TYR A 255 49.852 36.426 126.273 1.00 11.24 8 ATOM 916 C TYR A 255 42.143 35.929 128.227 1.00 8.29 6 ATOM 917 O TYR A 255 41.324 36.317 127.393 1.00 7.51 8 ATOM 918 N GLY A 256 41.819 35.279 129.347 1.00 8.20 7 ATOM 919 CA GLY A 256 40.457 34.859 129.637 1.00 8.20 6 ATOM 920 C GLY A 256 39.497 36.028 129.717 1.00 8.28 6 ATOM 921 O GLY A 256 38.421 35.970 129.132 1.00 8.77 8 ATOM 922 N ALA A 257 39.929 37.118 130.357 1.00 8.22 7 ATOM 923 CA ALA A 257 39.111 38.329 130.493 1.00 8.37 6 ATOM 924 CB ALA A 257 39.799 39.341 131.394 1.00 9.12 6 ATOM 925 C ALA A 257 38.799 38.961 129.141 1.00 9.17 6 ATOM 926 O ALA A 257 37.668 39.385 128.885 1.00 9.03 8 ATOM 927 N GLU A 258 39.793 38.960 128.256 1.00 9.45 7 ATOM 928 CA GLU A 258 39.626 39.518 126.917 1.00 9.23 6 ATOM 929 CB GLU A 258 40.982 39.762 126.263 1.00 10.32 6 ATOM 930 CG GLU A 258 41.842 40.737 127.063 1.00 10.32 6 ATOM 931 CD GLU A 258 42.976 41.347 126.274 1.00 12.97 6 ATOM 932 OE1 GLU A 258 43.488 40.711 125.333 1.00 12.51 8 ATOM 933 OE2 GLU A 258 43.356 42.494 126.594 1.00 13.09 8 ATOM 934 C GLU A 258 38.709 38.657 126.050 1.00 10.11 6 ATOM 935 O GLU A 258 37.889 39.192 125.298 1.00 10.13 8 ATOM 936 N ILE A 259 38.773 37.333 126.231 1.00 10.63 7 ATOM 937 CA ILE A 259 37.903 36.410 125.488 1.00 9.01 6 ATOM 938 CB ILE A 259 38.366 34.929 125.606 1.00 8.23 6 ATOM 939 CG2 ILE A 259 37.403 33.993 124.833 1.00 9.95 6 ATOM 940 CG1 ILE A 259 39.763 34.775 125.002 1.00 8.98 6 ATOM 941 CD1 ILE A 259 40.508 33.536 125.487 1.00 9.30 6 ATOM 942 C ILE A 259 36.454 36.560 125.988 1.00 8.43 6 ATOM 943 O ILE A 259 35.530 36.577 125.177 1.00 10.44 8 ATOM 944 N VAL A 260 36.278 36.742 127.303 1.00 7.99 7 ATOM 945 CA VAL A 260 34.946 36.924 127.900 1.00 7.71 6 ATOM 946 CB VAL A 260 34.994 36.958 129.466 1.00 8.74 6 ATOM 947 CG1 VAL A 260 33.630 37.300 130.062 1.00 10.31 6 ATOM 948 CG2 VAL A 260 35.419 35.625 130.011 1.00 10.15 6 ATOM 949 C VAL A 260 34.326 38.223 127.367 1.00 7.82 6 ATOM 950 O VAL A 260 33.156 38.239 126.999 1.00 9.47 8 ATOM 951 N SER A 261 35.139 39.279 127.268 1.00 9.11 7 ATOM 952 CA SER A 261 34.685 40.578 126.762 1.00 9.16 6 ATOM 953 CB SER A 261 35.817 41.609 126.846 1.00 10.75 6 ATOM 954 OG SER A 261 35.368 42.898 126.452 1.00 12.26 8 ATOM 955 C SER A 261 34.192 40.452 125.317 1.00 9.34 6 ATOM 956 O SER A 261 33.102 40.936 124.980 1.00 10.40 8 ATOM 957 N ALA A 262 34.951 39.707 124.508 1.00 9.96 7 ATOM 958 CA ALA A 262 34.616 39.478 123.102 1.00 9.29 6 ATOM 959 CB ALA A 262 35.784 38.842 122.383 1.00 9.41 6 ATOM 960 C ALA A 262 33.356 38.626 122.935 1.00 10.29 6 ATOM 961 O ALA A 262 32.518 38.928 122.087 1.00 10.48 8 ATOM 962 N LEU A 263 33.214 37.593 123.771 1.00 9.86 7 ATOM 963 CA LEU A 263 32.048 36.706 123.723 1.00 10.29 6 ATOM 964 CB LEU A 263 32.302 35.401 124.483 1.00 9.98 6 ATOM 965 CG LEU A 263 33.235 34.374 123.827 1.00 10.03 6 ATOM 966 CD1 LEU A 263 33.514 33.251 124.806 1.00 11.52 6 ATOM 967 CD2 LEU A 263 32.641 33.812 122.537 1.00 12.88 6 ATOM 968 C LEU A 263 30.777 37.398 124.215 1.00 11.30 6 ATOM 969 O LEU A 263 29.699 37.165 123.668 1.00 11.30 8 ATOM 970 N GLU A 264 30.926 38.300 125.192 1.00 11.15 7 ATOM 971 CA GLU A 264 29.807 39.087 125.728 1.00 11.33 6 ATOM 972 CB GLU A 264 30.273 39.982 126.895 1.00 13.74 6 ATOM 973 CG GLU A 264 29.160 40.738 127.668 1.00 19.62 6 ATOM 974 CD GLU A 264 28.794 42.099 127.093 1.00 25.17 6 ATOM 975 OE1 GLU A 264 27.580 42.378 126.974 1.00 28.22 8 ATOM 976 OE2 GLU A 264 29.711 42.880 126.758 1.00 29.46 8 ATOM 977 C GLU A 264 29.291 39.964 124.584 1.00 10.82 6 ATOM 978 O GLU A 264 28.081 40.063 124.371 1.00 11.30 8 ATOM 979 N TYR A 265 30.225 40.569 123.845 1.00 12.37 7 ATOM 980 CA TYR A 265 29.883 41.428 122.712 1.00 11.80 6 ATOM 981 CB TYR A 265 31.132 42.124 122.143 1.00 12.00 6 ATOM 982 CG TYR A 265 30.880 42.913 120.868 1.00 14.17 6 ATOM 983 CD1 TYR A 265 30.253 44.179 120.902 1.00 15.20 6 ATOM 984 CE1 TYR A 265 29.944 44.873 119.697 1.00 15.02 6 ATOM 985 CD2 TYR A 265 31.200 42.361 119.611 1.00 13.35 6 ATOM 986 CE2 TYR A 265 30.896 43.037 118.414 1.00 14.77 6 ATOM 987 CZ TYR A 265 30.270 44.283 118.463 1.00 15.02 6 ATOM 988 OH TYR A 265 29.957 44.896 117.277 1.00 16.50 8 ATOM 989 C TYR A 265 29.167 40.626 121.626 1.00 11.73 6 ATOM 990 O TYR A 265 28.129 41.063 121.128 1.00 12.82 8 ATOM 991 N LEU A 266 29.735 39.477 121.249 1.00 11.97 7 ATOM 992 CA LEU A 266 29.127 38.624 120.222 1.00 12.05 6 ATOM 993 CB LEU A 266 30.010 37.409 119.913 1.00 11.59 6 ATOM 994 CG LEU A 266 31.261 37.654 119.064 1.00 11.69 6 ATOM 995 CD1 LEU A 266 32.125 36.401 119.073 1.00 13.18 6 ATOM 996 CD2 LEU A 266 30.893 38.051 117.634 1.00 13.08 6 ATOM 997 C LEU A 266 27.717 38.182 120.604 1.00 11.87 6 ATOM 998 O LEU A 266 26.795 38.302 119.797 1.00 11.49 8 ATOM 999 N HIS A 267 27.533 37.786 121.867 1.00 10.93 7 ATOM 1000 CA HIS A 267 26.223 37.353 122.359 1.00 11.18 6 ATOM 1001 CB HIS A 267 26.346 36.670 123.726 1.00 10.66 6 ATOM 1002 CG HIS A 267 26.999 35.319 123.675 1.00 10.63 6 ATOM 1003 CD2 HIS A 267 27.619 34.657 122.666 1.00 11.09 6 ATOM 1004 ND1 HIS A 267 27.064 34.486 124.771 1.00 12.06 7 ATOM 1005 CE1 HIS A 267 27.691 33.372 124.443 1.00 10.44 6 ATOM 1006 NE2 HIS A 267 28.038 33.450 123.170 1.00 8.55 7 ATOM 1007 C HIS A 267 25.208 38.497 122.406 1.00 11.65 6 ATOM 1008 O HIS A 267 24.021 38.280 122.146 1.00 13.21 8 ATOM 1009 N SER A 268 25.695 39.720 122.640 1.00 13.70 7 ATOM 1010 CA SER A 268 24.837 40.913 122.682 1.00 14.73 6 ATOM 1011 CB SER A 268 25.562 42.097 123.341 1.00 15.25 6 ATOM 1012 OG SER A 268 26.495 42.711 122.469 1.00 19.13 8 ATOM 1013 C SER A 268 24.380 41.286 121.262 1.00 15.80 6 ATOM 1014 O SER A 268 23.369 41.971 121.087 1.00 17.35 8 ATOM 1015 N ARG A 269 25.141 40.820 120.267 1.00 15.44 7 ATOM 1016 CA ARG A 269 24.848 41.044 118.847 1.00 15.62 6 ATOM 1017 CB ARG A 269 26.145 41.312 118.065 1.00 18.82 6 ATOM 1018 CG ARG A 269 26.876 42.596 118.446 1.00 22.50 6 ATOM 1019 CD ARG A 269 26.221 43.847 117.875 1.00 26.13 6 ATOM 1020 NE ARG A 269 26.827 44.258 116.608 1.00 29.68 7 ATOM 1021 CZ ARG A 269 26.149 44.529 115.494 1.00 32.99 6 ATOM 1022 NH1 ARG A 269 24.822 44.436 115.468 1.00 35.14 7 ATOM 1023 NH2 ARG A 269 26.799 44.896 114.398 1.00 33.05 7 ATOM 1024 C ARG A 269 24.124 39.826 118.253 1.00 15.10 6 ATOM 1025 O ARG A 269 24.019 39.692 117.028 1.00 15.01 8 ATOM 1026 N ASP A 270 23.631 38.951 119.138 1.00 12.97 7 ATOM 1027 CA ASP A 270 22.902 37.719 118.792 1.00 13.07 6 ATOM 1028 CB ASP A 270 21.571 38.029 118.067 1.00 15.55 6 ATOM 1029 CG ASP A 270 20.628 38.900 118.885 1.00 18.49 6 ATOM 1030 OD1 ASP A 270 20.796 39.022 120.119 1.00 18.80 8 ATOM 1031 OD2 ASP A 270 19.691 39.454 118.278 1.00 19.66 8 ATOM 1032 C ASP A 270 23.720 36.701 117.984 1.00 12.41 6 ATOM 1033 O ASP A 270 23.180 35.949 117.169 1.00 12.29 8 ATOM 1034 N VAL A 271 25.030 36.692 118.220 1.00 11.56 7 ATOM 1035 CA VAL A 271 25.941 35.786 117.524 1.00 11.24 6 ATOM 1036 CB VAL A 271 27.086 36.576 116.795 1.00 11.07 6 ATOM 1037 CG1 VAL A 271 28.041 35.628 116.060 1.00 12.56 6 ATOM 1038 CG2 VAL A 271 26.506 37.589 115.808 1.00 12.97 6 ATOM 1039 C VAL A 271 26.575 34.785 118.487 1.00 11.13 6 ATOM 1040 O VAL A 271 27.059 35.165 119.549 1.00 13.72 8 ATOM 1041 N VAL A 272 26.528 33.505 118.118 1.00 10.75 7 ATOM 1042 CA VAL A 272 27.163 32.436 118.897 1.00 9.53 6 ATOM 1043 CB VAL A 272 26.211 31.241 119.147 1.00 9.39 6 ATOM 1044 CG1 VAL A 272 26.888 30.171 119.993 1.00 10.60 6 ATOM 1045 CG2 VAL A 272 25.003 31.719 119.872 1.00 11.64 6 ATOM 1046 C VAL A 272 28.349 32.027 118.028 1.00 10.46 6 ATOM 1047 O VAL A 272 28.191 31.735 116.845 1.00 11.34 8 ATOM 1048 N TYR A 273 29.530 32.008 118.638 1.00 10.17 7 ATOM 1049 CA TYR A 273 30.784 31.716 117.951 1.00 10.40 6 ATOM 1050 CB TYR A 273 31.922 32.326 118.776 1.00 10.32 6 ATOM 1051 CG TYR A 273 33.274 32.247 118.135 1.00 9.82 6 ATOM 1052 CD1 TYR A 273 33.599 33.010 116.994 1.00 11.78 6 ATOM 1053 CE1 TYR A 273 34.852 32.854 116.360 1.00 10.91 6 ATOM 1054 CD2 TYR A 273 34.223 31.352 118.626 1.00 9.97 6 ATOM 1055 CE2 TYR A 273 35.458 31.201 118.012 1.00 9.27 6 ATOM 1056 CZ TYR A 273 35.771 31.931 116.890 1.00 11.96 6 ATOM 1057 OH TYR A 273 36.981 31.665 116.319 1.00 12.28 8 ATOM 1058 C TYR A 273 31.041 30.245 117.559 1.00 11.40 6 ATOM 1059 O TYR A 273 31.550 29.976 116.463 1.00 10.69 8 ATOM 1060 N ARG A 274 30.739 29.325 118.481 1.00 11.09 7 ATOM 1061 CA ARG A 274 30.854 27.862 118.308 1.00 11.21 6 ATOM 1062 CB ARG A 274 29.832 27.352 117.269 1.00 11.92 6 ATOM 1063 CG ARG A 274 28.388 27.621 117.649 1.00 12.16 6 ATOM 1064 CD ARG A 274 27.404 26.886 116.765 1.00 11.71 6 ATOM 1065 NE ARG A 274 27.395 27.364 115.386 1.00 11.25 7 ATOM 1066 CZ ARG A 274 26.470 27.037 114.487 1.00 11.43 6 ATOM 1067 NH1 ARG A 274 25.470 26.231 114.819 1.00 12.81 7 ATOM 1068 NH2 ARG A 274 26.546 27.513 113.251 1.00 11.89 7 ATOM 1069 C ARG A 274 32.205 27.183 118.055 1.00 11.20 6 ATOM 1070 O ARG A 274 32.274 25.946 118.053 1.00 12.43 8 ATOM 1071 N ASP A 275 33.274 27.961 117.880 1.00 10.42 7 ATOM 1072 CA ASP A 275 34.584 27.366 117.611 1.00 10.31 6 ATOM 1073 CB ASP A 275 34.894 27.441 116.098 1.00 11.53 6 ATOM 1074 CG ASP A 275 35.938 26.414 115.648 1.00 11.03 6 ATOM 1075 OD1 ASP A 275 36.159 25.421 116.368 1.00 11.26 8 ATOM 1076 OD2 ASP A 275 36.543 26.609 114.573 1.00 11.21 8 ATOM 1077 C ASP A 275 35.747 27.920 118.449 1.00 9.71 6 ATOM 1078 O ASP A 275 36.847 28.132 117.926 1.00 11.05 8 ATOM 1079 N ILE A 276 35.508 28.192 119.738 1.00 10.17 7 ATOM 1080 CA ILE A 276 36.579 28.693 120.616 1.00 8.90 6 ATOM 1081 CB ILE A 276 36.075 29.076 122.053 1.00 9.50 6 ATOM 1082 CG2 ILE A 276 37.266 29.314 123.012 1.00 10.36 6 ATOM 1083 CG1 ILE A 276 35.159 30.308 122.021 1.00 10.78 6 ATOM 1084 CD1 ILE A 276 35.879 31.670 121.812 1.00 11.93 6 ATOM 1085 C ILE A 276 37.633 27.589 120.730 1.00 9.85 6 ATOM 1086 O ILE A 276 37.313 26.440 121.045 1.00 11.58 8 ATOM 1087 N LYS A 277 38.849 27.943 120.325 1.00 9.23 7 ATOM 1088 CA LYS A 277 40.007 27.066 120.369 1.00 8.29 6 ATOM 1089 CB LYS A 277 39.981 25.985 119.276 1.00 9.24 6 ATOM 1090 CG LYS A 277 39.972 26.423 117.855 1.00 8.24 6 ATOM 1091 CD LYS A 277 40.035 25.187 116.994 1.00 9.50 6 ATOM 1092 CE LYS A 277 39.871 25.524 115.542 1.00 11.54 6 ATOM 1093 NZ LYS A 277 39.785 24.276 114.736 1.00 11.88 7 ATOM 1094 C LYS A 277 41.283 27.868 120.313 1.00 7.92 6 ATOM 1095 O LYS A 277 41.282 28.996 119.826 1.00 9.72 8 ATOM 1096 N LEU A 278 42.378 27.280 120.792 1.00 7.68 7 ATOM 1097 CA LEU A 278 43.663 27.978 120.805 1.00 8.18 6 ATOM 1098 CB LEU A 278 44.714 27.140 121.522 1.00 8.71 6 ATOM 1099 CG LEU A 278 44.583 26.828 123.010 1.00 8.94 6 ATOM 1100 CD1 LEU A 278 45.706 25.886 123.348 1.00 9.56 6 ATOM 1101 CD2 LEU A 278 44.651 28.077 123.882 1.00 9.77 6 ATOM 1102 C LEU A 278 44.172 28.424 119.425 1.00 9.32 6 ATOM 1103 O LEU A 278 44.847 29.448 119.317 1.00 9.57 8 ATOM 1104 N GLU A 279 43.791 27.689 118.378 1.00 10.17 7 ATOM 1105 CA GLU A 279 44.190 28.007 117.000 1.00 10.11 6 ATOM 1106 CB GLU A 279 43.994 26.791 116.079 1.00 10.41 6 ATOM 1107 CG GLU A 279 44.888 25.588 116.396 1.00 12.00 6 ATOM 1108 CD GLU A 279 44.250 24.565 117.328 1.00 15.39 6 ATOM 1109 OE1 GLU A 279 43.406 24.937 118.171 1.00 14.16 8 ATOM 1110 OE2 GLU A 279 44.622 23.375 117.232 1.00 16.18 8 ATOM 1111 C GLU A 279 43.438 29.209 116.422 1.00 10.72 6 ATOM 1112 O GLU A 279 43.891 29.828 115.455 1.00 10.07 8 ATOM 1113 N ASN A 280 42.297 29.532 117.033 1.00 9.72 7 ATOM 1114 CA ASN A 280 41.450 30.649 116.606 1.00 9.62 6 ATOM 1115 CB ASN A 280 39.972 30.243 116.629 1.00 8.79 6 ATOM 1116 CG ASN A 280 39.606 29.282 115.520 1.00 10.79 6 ATOM 1117 OD1 ASN A 280 40.431 28.950 114.665 1.00 9.20 8 ATOM 1118 ND2 ASN A 280 38.361 28.820 115.532 1.00 9.71 7 ATOM 1119 C ASN A 280 41.628 31.902 117.457 1.00 8.78 6 ATOM 1120 O ASN A 280 40.978 32.920 117.204 1.00 9.62 8 ATOM 1121 N LEU A 281 42.465 31.804 118.492 1.00 9.00 7 ATOM 1122 CA LEU A 281 42.736 32.923 119.396 1.00 8.61 6 ATOM 1123 CB LEU A 281 42.584 32.494 120.863 1.00 8.74 6 ATOM 1124 CG LEU A 281 41.199 31.974 121.280 1.00 7.84 6 ATOM 1125 CD1 LEU A 281 41.287 31.256 122.612 1.00 9.65 6 ATOM 1126 CD2 LEU A 281 40.173 33.092 121.327 1.00 9.93 6 ATOM 1127 C LEU A 281 44.137 33.442 119.114 1.00 9.65 6 ATOM 1128 O LEU A 281 45.136 32.774 119.384 1.00 12.34 8 ATOM 1129 N MET A 282 44.187 34.621 118.509 1.00 10.43 7 ATOM 1130 CA MET A 282 45.444 35.246 118.127 1.00 10.65 6 ATOM 1131 CB MET A 282 45.329 35.847 116.725 1.00 11.51 6 ATOM 1132 CG MET A 282 44.652 35.008 115.666 1.00 15.05 6 ATOM 1133 SD MET A 282 45.488 33.477 115.326 1.00 16.17 16 ATOM 1134 CE MET A 282 46.894 34.070 114.414 1.00 17.11 6 ATOM 1135 C MET A 282 45.844 36.371 119.052 1.00 10.69 6 ATOM 1136 O MET A 282 45.055 36.820 119.882 1.00 10.89 8 ATOM 1137 N LEU A 283 47.093 36.805 118.906 1.00 10.61 7 ATOM 1138 CA LEU A 283 47.621 37.935 119.658 1.00 11.06 6 ATOM 1139 CB LEU A 283 48.844 37.542 120.499 1.00 12.62 6 ATOM 1140 CG LEU A 283 48.673 36.635 121.723 1.00 11.37 6 ATOM 1141 CD1 LEU A 283 49.996 36.537 122.464 1.00 12.97 6 ATOM 1142 CD2 LEU A 283 47.597 37.183 122.652 1.00 13.21 6 ATOM 1143 C LEU A 283 48.018 39.004 118.649 1.00 11.28 6 ATOM 1144 O LEU A 283 48.588 38.678 117.602 1.00 10.74 8 ATOM 1145 N ASP A 284 47.645 40.259 118.912 1.00 12.10 7 ATOM 1146 CA ASP A 284 48.039 41.352 118.019 1.00 12.66 6 ATOM 1147 CB ASP A 284 47.022 42.525 118.019 1.00 12.34 6 ATOM 1148 CG ASP A 284 46.860 43.225 119.375 1.00 15.48 6 ATOM 1149 OD1 ASP A 284 47.685 43.057 120.297 1.00 14.93 8 ATOM 1150 OD2 ASP A 284 45.877 43.987 119.503 1.00 15.81 8 ATOM 1151 C ASP A 284 49.465 41.799 118.370 1.00 13.20 6 ATOM 1152 O ASP A 284 50.088 41.218 119.272 1.00 12.57 8 ATOM 1153 N LYS A 285 49.962 42.835 117.692 1.00 14.19 7 ATOM 1154 CA LYS A 285 51.318 43.351 117.924 1.00 17.16 6 ATOM 1155 CB LYS A 285 51.671 44.433 116.890 1.00 19.25 6 ATOM 1156 CG LYS A 285 50.663 45.571 116.748 1.00 24.70 6 ATOM 1157 CD LYS A 285 50.967 46.405 115.509 1.00 28.43 6 ATOM 1158 CE LYS A 285 49.821 47.341 115.168 1.00 31.27 6 ATOM 1159 NZ LYS A 285 50.059 48.053 113.882 1.00 33.40 7 ATOM 1160 C LYS A 285 51.598 43.853 119.346 1.00 15.69 6 ATOM 1161 O LYS A 285 52.747 43.865 119.785 1.00 17.81 8 ATOM 1162 N ASP A 286 50.531 44.187 120.072 1.00 15.16 7 ATOM 1163 CA ASP A 286 50.632 44.684 121.443 1.00 15.05 6 ATOM 1164 CB ASP A 286 49.596 45.787 121.681 1.00 15.77 6 ATOM 1165 CG ASP A 286 49.817 47.006 120.791 1.00 19.87 6 ATOM 1166 OD1 ASP A 286 50.984 47.428 120.626 1.00 21.80 8 ATOM 1167 OD2 ASP A 286 48.822 47.537 120.252 1.00 22.84 8 ATOM 1168 C ASP A 286 50.480 43.583 122.495 1.00 15.14 6 ATOM 1169 O ASP A 286 50.821 43.788 123.659 1.00 15.75 8 ATOM 1170 N GLY A 287 49.974 42.422 122.076 1.00 14.04 7 ATOM 1171 CA GLY A 287 49.785 41.306 122.993 1.00 12.92 6 ATOM 1172 C GLY A 287 48.360 41.080 123.452 1.00 11.89 6 ATOM 1173 O GLY A 287 48.127 40.309 124.385 1.00 11.67 8 ATOM 1174 N HIS A 288 47.415 41.773 122.820 1.00 11.23 7 ATOM 1175 CA HIS A 288 45.999 41.629 123.144 1.00 11.93 6 ATOM 1176 CB HIS A 288 45.244 42.935 122.900 1.00 13.05 6 ATOM 1177 CG HIS A 288 45.558 44.011 123.885 1.00 14.87 6 ATOM 1178 CD2 HIS A 288 46.274 45.154 123.759 1.00 16.12 6 ATOM 1179 ND1 HIS A 288 45.097 43.988 125.183 1.00 14.48 7 ATOM 1180 CE1 HIS A 288 45.514 45.071 125.815 1.00 17.06 6 ATOM 1181 NE2 HIS A 288 46.230 45.795 124.973 1.00 16.14 7 ATOM 1182 C HIS A 288 45.388 40.543 122.275 1.00 10.67 6 ATOM 1183 O HIS A 288 45.855 40.296 121.165 1.00 10.57 8 ATOM 1184 N ILE A 289 44.329 39.915 122.783 1.00 10.61 7 ATOM 1185 CA ILE A 289 43.611 38.858 122.069 1.00 10.93 6 ATOM 1186 CB ILE A 289 42.575 38.145 123.027 1.00 9.92 6 ATOM 1187 CG2 ILE A 289 41.484 37.347 122.265 1.00 10.20 6 ATOM 1188 CG1 ILE A 289 43.300 37.256 124.043 1.00 11.79 6 ATOM 1189 CD1 ILE A 289 43.927 35.980 123.487 1.00 12.33 6 ATOM 1190 C ILE A 289 42.874 39.405 120.842 1.00 9.93 6 ATOM 1191 O ILE A 289 42.372 40.531 120.853 1.00 10.71 8 ATOM 1192 N LYS A 290 42.903 38.618 119.770 1.00 11.19 7 ATOM 1193 CA LYS A 290 42.183 38.907 118.541 1.00 11.55 6 ATOM 1194 CB LYS A 290 43.094 39.423 117.413 1.00 12.00 6 ATOM 1195 CG LYS A 290 43.451 40.906 117.479 1.00 13.97 6 ATOM 1196 CD LYS A 290 42.235 41.811 117.312 1.00 17.20 6 ATOM 1197 CE LYS A 290 42.632 43.271 117.247 1.00 22.39 6 ATOM 1198 NZ LYS A 290 41.430 44.147 117.108 1.00 25.85 7 ATOM 1199 C LYS A 290 41.556 37.578 118.145 1.00 11.00 6 ATOM 1200 O LYS A 290 42.261 36.634 117.787 1.00 12.44 8 ATOM 1201 N ILE A 291 40.241 37.468 118.309 1.00 11.01 7 ATOM 1202 CA ILE A 291 39.550 36.242 117.920 1.00 10.30 6 ATOM 1203 CB ILE A 291 38.139 36.116 118.575 1.00 11.12 6 ATOM 1204 CG2 ILE A 291 37.412 34.874 118.045 1.00 13.36 6 ATOM 1205 CG1 ILE A 291 38.253 36.089 120.106 1.00 10.32 6 ATOM 1206 CD1 ILE A 291 36.960 35.736 120.850 1.00 12.30 6 ATOM 1207 C ILE A 291 39.409 36.286 116.398 1.00 11.06 6 ATOM 1208 O ILE A 291 39.035 37.317 115.841 1.00 11.10 8 ATOM 1209 N THR A 292 39.802 35.199 115.742 1.00 10.40 7 ATOM 1210 CA THR A 292 39.687 35.097 114.296 1.00 10.07 6 ATOM 1211 CB THR A 292 41.077 35.002 113.610 1.00 10.90 6 ATOM 1212 OG1 THR A 292 40.924 35.271 112.210 1.00 12.93 8 ATOM 1213 CG2 THR A 292 41.722 33.614 113.806 1.00 12.70 6 ATOM 1214 C THR A 292 38.818 33.882 113.983 1.00 11.07 6 ATOM 1215 O THR A 292 38.337 33.224 114.904 1.00 12.85 8 ATOM 1216 N ASP A 293 38.626 33.599 112.692 1.00 10.36 7 ATOM 1217 CA ASP A 293 37.830 32.461 112.207 1.00 10.58 6 ATOM 1218 CB ASP A 293 38.545 31.132 112.540 1.00 9.95 6 ATOM 1219 CG ASP A 293 37.878 29.913 111.918 1.00 9.97 6 ATOM 1220 OD1 ASP A 293 36.931 30.053 111.109 1.00 11.71 8 ATOM 1221 OD2 ASP A 293 38.297 28.791 112.259 1.00 11.39 8 ATOM 1222 C ASP A 293 36.371 32.461 112.686 1.00 11.46 6 ATOM 1223 O ASP A 293 36.004 31.756 113.629 1.00 11.27 8 ATOM 1224 N PHE A 294 35.540 33.210 111.971 1.00 11.14 7 ATOM 1225 CA PHE A 294 34.119 33.316 112.280 1.00 11.42 6 ATOM 1226 CB PHE A 294 33.687 34.783 112.137 1.00 11.24 6 ATOM 1227 CG PHE A 294 34.389 35.706 113.098 1.00 13.15 6 ATOM 1228 CD1 PHE A 294 35.604 36.323 112.743 1.00 13.88 6 ATOM 1229 CD2 PHE A 294 33.866 35.929 114.384 1.00 13.77 6 ATOM 1230 CE1 PHE A 294 36.300 37.155 113.658 1.00 15.10 6 ATOM 1231 CE2 PHE A 294 34.544 36.757 115.317 1.00 15.04 6 ATOM 1232 CZ PHE A 294 35.769 37.373 114.950 1.00 14.92 6 ATOM 1233 C PHE A 294 33.306 32.385 111.373 1.00 12.18 6 ATOM 1234 O PHE A 294 32.102 32.579 111.175 1.00 12.31 8 ATOM 1235 N GLY A 295 33.984 31.339 110.892 1.00 12.53 7 ATOM 1236 CA GLY A 295 33.420 30.349 109.985 1.00 12.76 6 ATOM 1237 C GLY A 295 32.275 29.472 110.430 1.00 13.30 6 ATOM 1238 O GLY A 295 31.606 28.866 109.586 1.00 13.81 8 ATOM 1239 N LEU A 296 32.088 29.347 111.741 1.00 12.35 7 ATOM 1240 CA LEU A 296 31.005 28.533 112.282 1.00 11.62 6 ATOM 1241 CB LEU A 296 31.552 27.313 113.042 1.00 11.39 6 ATOM 1242 CG LEU A 296 32.155 26.170 112.206 1.00 13.45 6 ATOM 1243 CD1 LEU A 296 32.690 25.106 113.118 1.00 12.66 6 ATOM 1244 CD2 LEU A 296 31.126 25.574 111.241 1.00 13.98 6 ATOM 1245 C LEU A 296 30.022 29.327 113.134 1.00 12.78 6 ATOM 1246 O LEU A 296 29.216 28.749 113.864 1.00 13.00 8 ATOM 1247 N CYS A 297 30.057 30.654 112.993 1.00 12.11 7 ATOM 1248 CA CYS A 297 29.157 31.544 113.727 1.00 14.09 6 ATOM 1249 CB CYS A 297 29.561 33.008 113.539 1.00 13.17 6 ATOM 1250 SG CYS A 297 30.983 33.555 114.500 1.00 15.37 16 ATOM 1251 C CYS A 297 27.711 31.391 113.273 1.00 15.46 6 ATOM 1252 O CYS A 297 27.447 30.988 112.136 1.00 17.26 8 ATOM 1253 N LYS A 298 26.784 31.647 114.190 1.00 14.89 7 ATOM 1254 CA LYS A 298 25.364 31.594 113.876 1.00 14.68 6 ATOM 1255 CB LYS A 298 24.678 30.422 114.588 1.00 15.71 6 ATOM 1256 CG LYS A 298 23.260 30.112 114.080 1.00 16.39 6 ATOM 1257 CD LYS A 298 23.236 29.443 112.713 1.00 18.38 6 ATOM 1258 CE LYS A 298 21.800 29.224 112.259 1.00 20.56 6 ATOM 1259 NZ LYS A 298 21.733 28.614 110.901 1.00 22.67 7 ATOM 1260 C LYS A 298 24.764 32.920 114.322 1.00 15.11 6 ATOM 1261 O LYS A 298 24.996 33.366 115.446 1.00 15.14 8 ATOM 1262 N GLU A 299 24.045 33.568 113.408 1.00 15.60 7 ATOM 1263 CA GLU A 299 23.389 34.851 113.676 1.00 16.02 6 ATOM 1264 CB GLU A 299 23.355 35.713 112.411 1.00 18.14 6 ATOM 1265 CG GLU A 299 24.693 36.203 111.913 1.00 19.83 6 ATOM 1266 CD GLU A 299 24.567 36.917 110.579 1.00 21.36 6 ATOM 1267 OE1 GLU A 299 24.486 38.161 110.572 1.00 24.32 8 ATOM 1268 OE2 GLU A 299 24.530 36.228 109.539 1.00 23.28 8 ATOM 1269 C GLU A 299 21.951 34.645 114.136 1.00 16.19 6 ATOM 1270 O GLU A 299 21.397 33.549 113.998 1.00 16.20 8 ATOM 1271 N GLY A 300 21.361 35.716 114.670 1.00 15.37 7 ATOM 1272 CA GLY A 300 19.979 35.706 115.128 1.00 15.60 6 ATOM 1273 C GLY A 300 19.649 34.854 116.338 1.00 16.36 6 ATOM 1274 O GLY A 300 18.510 34.404 116.485 1.00 17.71 8 ATOM 1275 N ILE A 301 20.648 34.608 117.186 1.00 14.10 7 ATOM 1276 CA ILE A 301 20.469 33.798 118.387 1.00 15.25 6 ATOM 1277 CB ILE A 301 21.582 32.694 118.517 1.00 15.05 6 ATOM 1278 CG2 ILE A 301 21.308 31.767 119.715 1.00 16.63 6 ATOM 1279 CG1 ILE A 301 21.724 31.881 117.220 1.00 15.98 6 ATOM 1280 CD1 ILE A 301 20.454 31.157 116.727 1.00 17.28 6 ATOM 1281 C ILE A 301 20.421 34.690 119.630 1.00 17.23 6 ATOM 1282 O ILE A 301 21.450 34.978 120.250 1.00 17.80 8 ATOM 1283 N SER A 302 19.215 35.160 119.949 1.00 17.90 7 ATOM 1284 CA SER A 302 18.978 36.025 121.104 1.00 20.36 6 ATOM 1285 CB SER A 302 17.955 37.112 120.761 1.00 21.51 6 ATOM 1286 OG SER A 302 16.768 36.553 120.224 1.00 25.90 8 ATOM 1287 C SER A 302 18.477 35.240 122.299 1.00 22.09 6 ATOM 1288 O SER A 302 17.729 34.278 122.141 1.00 21.86 8 ATOM 1289 N ASP A 303 18.876 35.690 123.492 1.00 23.86 7 ATOM 1290 CA ASP A 303 18.496 35.098 124.783 1.00 25.72 6 ATOM 1291 CB ASP A 303 17.054 35.505 125.178 1.00 29.08 6 ATOM 1292 CG ASP A 303 16.783 37.008 125.022 1.00 33.78 6 ATOM 1293 OD1 ASP A 303 17.701 37.828 125.244 1.00 35.23 8 ATOM 1294 OD2 ASP A 303 15.635 37.363 124.667 1.00 36.15 8 ATOM 1295 C ASP A 303 18.684 33.569 124.840 1.00 24.36 6 ATOM 1296 O ASP A 303 19.817 33.080 124.761 1.00 25.34 8 ATOM 1297 N GLY A 304 17.573 32.831 124.884 1.00 22.09 7 ATOM 1298 CA GLY A 304 17.619 31.380 124.944 1.00 20.47 6 ATOM 1299 C GLY A 304 17.348 30.654 123.637 1.00 20.10 6 ATOM 1300 O GLY A 304 16.982 29.474 123.660 1.00 19.90 8 ATOM 1301 N ALA A 305 17.547 31.333 122.501 1.00 18.99 7 ATOM 1302 CA ALA A 305 17.331 30.739 121.173 1.00 16.01 6 ATOM 1303 CB ALA A 305 17.443 31.793 120.083 1.00 16.36 6 ATOM 1304 C ALA A 305 18.308 29.594 120.915 1.00 16.73 6 ATOM 1305 O ALA A 305 19.424 29.582 121.450 1.00 15.24 8 ATOM 1306 N THR A 306 17.878 28.629 120.107 1.00 16.36 7 ATOM 1307 CA THR A 306 18.688 27.449 119.831 1.00 17.05 6 ATOM 1308 CB THR A 306 17.953 26.180 120.293 1.00 18.88 6 ATOM 1309 OG1 THR A 306 16.707 26.068 119.598 1.00 20.34 8 ATOM 1310 CG2 THR A 306 17.703 26.185 121.807 1.00 19.27 6 ATOM 1311 C THR A 306 19.185 27.237 118.396 1.00 16.69 6 ATOM 1312 O THR A 306 18.692 27.863 117.454 1.00 16.41 8 ATOM 1313 N MET A 307 20.190 26.362 118.269 1.00 15.50 7 ATOM 1314 CA MET A 307 20.840 25.987 117.001 1.00 14.79 6 ATOM 1315 CB MET A 307 22.292 26.459 116.986 1.00 14.74 6 ATOM 1316 CG MET A 307 22.469 27.948 117.124 1.00 15.40 6 ATOM 1317 SD MET A 307 23.980 28.386 117.965 1.00 14.26 16 ATOM 1318 CE MET A 307 23.453 28.236 119.604 1.00 16.72 6 ATOM 1319 C MET A 307 20.833 24.464 116.864 1.00 15.85 6 ATOM 1320 O MET A 307 20.878 23.760 117.869 1.00 16.29 8 ATOM 1321 N LYS A 308 20.840 23.965 115.625 1.00 15.35 7 ATOM 1322 CA LYS A 308 20.798 22.522 115.365 1.00 18.66 6 ATOM 1323 CB LYS A 308 19.511 22.159 114.603 1.00 21.77 6 ATOM 1324 CG LYS A 308 18.228 22.270 115.421 1.00 28.35 6 ATOM 1325 CD LYS A 308 17.019 21.762 114.654 1.00 32.57 6 ATOM 1326 CE LYS A 308 15.754 21.876 115.494 1.00 34.93 6 ATOM 1327 NZ LYS A 308 14.565 21.322 114.788 1.00 36.57 7 ATOM 1328 C LYS A 308 21.991 21.895 114.642 1.00 17.94 6 ATOM 1329 O LYS A 308 22.148 20.670 114.670 1.00 19.44 8 ATOM 1330 N PTH A 309 22.846 22.717 114.031 1.00 17.40 7 ATOM 1331 CA PTH A 309 23.997 22.217 113.272 1.00 15.65 6 ATOM 1332 CB PTH A 309 24.682 23.358 112.490 1.00 15.20 6 ATOM 1333 OG1 PTH A 309 23.712 24.090 111.721 1.00 16.08 8 ATOM 1334 CG2 PTH A 309 25.736 22.807 111.519 1.00 15.11 6 ATOM 1335 C PTH A 309 25.049 21.500 114.136 1.00 15.97 6 ATOM 1336 O PTH A 309 25.526 22.062 115.122 1.00 15.03 8 ATOM 1337 P PTH A 309 23.568 25.460 111.873 1.00 15.53 15 ATOM 1338 O1P PTH A 309 24.752 26.248 111.399 1.00 18.09 8 ATOM 1339 O2P PTH A 309 23.158 25.593 113.310 1.00 15.00 8 ATOM 1340 O3P PTH A 309 22.429 25.765 110.829 1.00 18.47 8 ATOM 1341 N PHE A 310 25.397 20.267 113.767 1.00 15.09 7 ATOM 1342 CA PHE A 310 26.423 19.504 114.485 1.00 14.34 6 ATOM 1343 CB PHE A 310 26.227 17.991 114.247 1.00 14.10 6 ATOM 1344 CG PHE A 310 27.223 17.094 114.967 1.00 16.32 6 ATOM 1345 CD1 PHE A 310 27.689 15.925 114.335 1.00 17.96 6 ATOM 1346 CD2 PHE A 310 27.672 17.380 116.278 1.00 16.41 6 ATOM 1347 CE1 PHE A 310 28.590 15.042 114.992 1.00 18.61 6 ATOM 1348 CE2 PHE A 310 28.574 16.509 116.953 1.00 16.19 6 ATOM 1349 CZ PHE A 310 29.034 15.336 116.306 1.00 18.26 6 ATOM 1350 C PHE A 310 27.745 20.012 113.903 1.00 14.54 6 ATOM 1351 O PHE A 310 28.137 19.636 112.796 1.00 14.23 8 ATOM 1352 N CYS A 311 28.382 20.925 114.638 1.00 13.11 7 ATOM 1353 CA CYS A 311 29.632 21.538 114.199 1.00 13.41 6 ATOM 1354 CB CYS A 311 29.330 22.730 113.283 1.00 13.50 6 ATOM 1355 SG CYS A 311 28.514 24.101 114.103 1.00 13.37 16 ATOM 1356 C CYS A 311 30.509 22.003 115.359 1.00 13.00 6 ATOM 1357 O CYS A 311 30.055 22.078 116.499 1.00 12.35 8 ATOM 1358 N GLY A 312 31.744 22.375 115.025 1.00 12.88 7 ATOM 1359 CA GLY A 312 32.712 22.837 116.008 1.00 12.86 6 ATOM 1360 C GLY A 312 34.022 22.129 115.734 1.00 12.33 6 ATOM 1361 O GLY A 312 34.299 21.770 114.598 1.00 13.15 8 ATOM 1362 N THR A 313 34.843 21.966 116.763 1.00 11.86 7 ATOM 1363 CA THR A 313 36.117 21.259 116.645 1.00 10.14 6 ATOM 1364 CB THR A 313 37.301 22.206 116.956 1.00 10.44 6 ATOM 1365 OG1 THR A 313 37.436 23.145 115.884 1.00 10.80 8 ATOM 1366 CG2 THR A 313 38.583 21.453 117.065 1.00 11.08 6 ATOM 1367 C THR A 313 35.968 20.114 117.651 1.00 11.70 6 ATOM 1368 O THR A 313 35.642 20.372 118.807 1.00 10.74 8 ATOM 1369 N PRO A 314 36.205 18.842 117.228 1.00 11.54 7 ATOM 1370 CD PRO A 314 36.736 18.435 115.909 1.00 12.43 6 ATOM 1371 CA PRO A 314 36.077 17.650 118.081 1.00 12.23 6 ATOM 1372 CB PRO A 314 36.840 16.591 117.294 1.00 12.24 6 ATOM 1373 CG PRO A 314 36.509 16.940 115.913 1.00 12.53 6 ATOM 1374 C PRO A 314 36.491 17.712 119.547 1.00 11.90 6 ATOM 1375 O PRO A 314 35.671 17.476 120.436 1.00 12.58 8 ATOM 1376 N GLU A 315 37.726 18.139 119.790 1.00 11.73 7 ATOM 1377 CA GLU A 315 38.294 18.232 121.139 1.00 11.65 6 ATOM 1378 CB GLU A 315 39.805 18.469 121.028 1.00 13.25 6 ATOM 1379 CG GLU A 315 40.616 17.282 120.459 1.00 14.19 6 ATOM 1380 CD GLU A 315 40.638 17.168 118.931 1.00 16.37 6 ATOM 1381 OE1 GLU A 315 40.041 18.007 118.221 1.00 14.23 8 ATOM 1382 OE2 GLU A 315 41.290 16.225 118.433 1.00 18.21 8 ATOM 1383 C GLU A 315 37.667 19.298 122.036 1.00 10.25 6 ATOM 1384 O GLU A 315 37.786 19.235 123.264 1.00 12.56 8 ATOM 1385 N TYR A 316 36.955 20.232 121.408 1.00 11.11 7 ATOM 1386 CA TYR A 316 36.316 21.359 122.081 1.00 10.65 6 ATOM 1387 CB TYR A 316 36.717 22.655 121.371 1.00 10.98 6 ATOM 1388 CG TYR A 316 38.160 23.037 121.567 1.00 10.60 6 ATOM 1389 CD1 TYR A 316 39.181 22.485 120.764 1.00 10.05 6 ATOM 1390 CE1 TYR A 316 40.542 22.844 120.962 1.00 9.96 6 ATOM 1391 CD2 TYR A 316 38.516 23.949 122.566 1.00 11.26 6 ATOM 1392 CE2 TYR A 316 39.864 24.316 122.779 1.00 8.34 6 ATOM 1393 CZ TYR A 316 40.865 23.767 121.968 1.00 9.90 6 ATOM 1394 OH TYR A 316 42.145 24.230 122.112 1.00 9.37 8 ATOM 1395 C TYR A 316 34.799 21.314 122.168 1.00 11.13 6 ATOM 1396 O TYR A 316 34.194 22.219 122.746 1.00 10.57 8 ATOM 1397 N LEU A 317 34.183 20.281 121.594 1.00 10.04 7 ATOM 1398 CA LEU A 317 32.726 20.161 121.603 1.00 11.08 6 ATOM 1399 CB LEU A 317 32.266 18.970 120.761 1.00 11.22 6 ATOM 1400 CG LEU A 317 32.467 19.008 119.253 1.00 13.09 6 ATOM 1401 CD1 LEU A 317 31.974 17.699 118.683 1.00 14.17 6 ATOM 1402 CD2 LEU A 317 31.748 20.176 118.617 1.00 14.11 6 ATOM 1403 C LEU A 317 32.121 20.027 122.981 1.00 10.03 6 ATOM 1404 O LEU A 317 32.657 19.324 123.836 1.00 9.84 8 ATOM 1405 N ALA A 318 31.028 20.759 123.190 1.00 9.60 7 ATOM 1406 CA ALA A 318 30.273 20.734 124.436 1.00 9.90 6 ATOM 1407 CB ALA A 318 29.371 21.966 124.508 1.00 9.34 6 ATOM 1408 C ALA A 318 29.451 19.441 124.472 1.00 10.07 6 ATOM 1409 O ALA A 318 29.060 18.947 123.415 1.00 11.23 8 ATOM 1410 N PRO A 319 29.224 18.847 125.671 1.00 10.24 7 ATOM 1411 CD PRO A 319 29.707 19.251 126.999 1.00 11.91 6 ATOM 1412 CA PRO A 319 28.445 17.607 125.798 1.00 11.42 6 ATOM 1413 CB PRO A 319 28.318 17.442 127.309 1.00 13.43 6 ATOM 1414 CG PRO A 319 29.601 17.967 127.784 1.00 13.39 6 ATOM 1415 C PRO A 319 27.076 17.640 125.132 1.00 12.32 6 ATOM 1416 O PRO A 319 26.692 16.672 124.481 1.00 12.64 8 ATOM 1417 N GLU A 320 26.385 18.780 125.231 1.00 12.71 7 ATOM 1418 CA GLU A 320 25.056 18.940 124.629 1.00 11.42 6 ATOM 1419 CB GLU A 320 24.358 20.216 125.141 1.00 11.32 6 ATOM 1420 CG GLU A 320 25.017 21.549 124.753 1.00 11.27 6 ATOM 1421 CD GLU A 320 26.027 22.078 125.756 1.00 14.01 6 ATOM 1422 OE1 GLU A 320 26.666 21.289 126.493 1.00 10.84 8 ATOM 1423 OE2 GLU A 320 26.208 23.317 125.784 1.00 13.57 8 ATOM 1424 C GLU A 320 25.084 18.882 123.091 1.00 11.89 6 ATOM 1425 O GLU A 320 24.112 18.447 122.469 1.00 11.84 8 ATOM 1426 N VAL A 321 26.220 19.259 122.493 1.00 10.09 7 ATOM 1427 CA VAL A 321 26.386 19.222 121.032 1.00 9.77 6 ATOM 1428 CB VAL A 321 27.582 20.115 120.554 1.00 10.34 6 ATOM 1429 CG1 VAL A 321 27.720 20.112 119.022 1.00 11.92 6 ATOM 1430 CG2 VAL A 321 27.366 21.540 121.020 1.00 11.02 6 ATOM 1431 C VAL A 321 26.564 17.763 120.586 1.00 10.88 6 ATOM 1432 O VAL A 321 26.245 17.412 119.452 1.00 12.29 8 ATOM 1433 N LEU A 322 27.007 16.913 121.515 1.00 10.49 7 ATOM 1434 CA LEU A 322 27.200 15.486 121.248 1.00 10.52 6 ATOM 1435 CB LEU A 322 28.380 14.958 122.054 1.00 11.29 6 ATOM 1436 CG LEU A 322 29.719 15.466 121.534 1.00 11.46 6 ATOM 1437 CD1 LEU A 322 30.799 15.145 122.528 1.00 9.97 6 ATOM 1438 CD2 LEU A 322 29.998 14.836 120.186 1.00 11.90 6 ATOM 1439 C LEU A 322 25.937 14.670 121.518 1.00 10.41 6 ATOM 1440 O LEU A 322 25.950 13.428 121.510 1.00 11.21 8 ATOM 1441 N GLU A 323 24.851 15.393 121.769 1.00 11.88 7 ATOM 1442 CA GLU A 323 23.537 14.809 122.004 1.00 13.48 6 ATOM 1443 CB GLU A 323 22.949 15.291 123.331 1.00 13.70 6 ATOM 1444 CG GLU A 323 23.685 14.788 124.564 1.00 12.40 6 ATOM 1445 CD GLU A 323 23.174 15.399 125.851 1.00 15.22 6 ATOM 1446 OE1 GLU A 323 22.629 16.524 125.815 1.00 15.12 8 ATOM 1447 OE2 GLU A 323 23.326 14.753 126.909 1.00 15.11 8 ATOM 1448 C GLU A 323 22.644 15.241 120.850 1.00 15.42 6 ATOM 1449 O GLU A 323 22.977 16.189 120.130 1.00 16.80 8 ATOM 1450 N ASP A 324 21.535 14.528 120.649 1.00 16.33 7 ATOM 1451 CA ASP A 324 20.589 14.852 119.579 1.00 19.00 6 ATOM 1452 CB ASP A 324 19.552 13.734 119.400 1.00 20.11 6 ATOM 1453 CG ASP A 324 20.141 12.454 118.842 1.00 22.07 6 ATOM 1454 OD1 ASP A 324 21.112 12.506 118.055 1.00 23.00 8 ATOM 1455 OD2 ASP A 324 19.595 11.384 119.175 1.00 22.41 8 ATOM 1456 C ASP A 324 19.847 16.156 119.858 1.00 18.96 6 ATOM 1457 O ASP A 324 19.842 16.655 120.987 1.00 19.77 8 ATOM 1458 N ASN A 325 19.216 16.678 118.806 1.00 20.60 7 ATOM 1459 CA ASN A 325 18.422 17.907 118.811 1.00 22.36 6 ATOM 1460 CB ASN A 325 17.245 17.828 119.821 1.00 25.74 6 ATOM 1461 CG ASN A 325 16.030 18.656 119.391 1.00 28.96 6 ATOM 1462 OD1 ASN A 325 15.400 19.320 120.214 1.00 32.51 8 ATOM 1463 ND2 ASN A 325 15.705 18.619 118.101 1.00 30.63 7 ATOM 1464 C ASN A 325 19.228 19.211 118.923 1.00 22.42 6 ATOM 1465 O ASN A 325 20.364 19.290 118.443 1.00 23.68 8 ATOM 1466 N ASP A 326 18.654 20.204 119.593 1.00 20.82 7 ATOM 1467 CA ASP A 326 19.243 21.531 119.701 1.00 19.49 6 ATOM 1468 CB ASP A 326 18.142 22.562 119.414 1.00 21.18 6 ATOM 1469 CG ASP A 326 16.942 22.462 120.371 1.00 24.95 6 ATOM 1470 OD1 ASP A 326 16.944 21.627 121.303 1.00 27.27 8 ATOM 1471 OD2 ASP A 326 15.993 23.255 120.189 1.00 26.25 8 ATOM 1472 C ASP A 326 20.061 21.934 120.931 1.00 17.48 6 ATOM 1473 O ASP A 326 20.029 21.269 121.964 1.00 18.57 8 ATOM 1474 N TYR A 327 20.784 23.047 120.799 1.00 15.53 7 ATOM 1475 CA TYR A 327 21.622 23.588 121.872 1.00 14.32 6 ATOM 1476 CB TYR A 327 23.065 23.035 121.775 1.00 12.75 6 ATOM 1477 CG TYR A 327 23.763 23.262 120.448 1.00 11.27 6 ATOM 1478 CD1 TYR A 327 24.490 24.450 120.206 1.00 10.00 6 ATOM 1479 CE1 TYR A 327 25.087 24.704 118.960 1.00 11.46 6 ATOM 1480 CD2 TYR A 327 23.660 22.319 119.403 1.00 11.88 6 ATOM 1481 CE2 TYR A 327 24.258 22.563 118.138 1.00 11.89 6 ATOM 1482 CZ TYR A 327 24.966 23.767 117.933 1.00 12.28 6 ATOM 1483 OH TYR A 327 25.508 24.058 116.710 1.00 14.22 8 ATOM 1484 C TYR A 327 21.624 25.118 121.854 1.00 14.21 6 ATOM 1485 O TYR A 327 21.402 25.725 120.806 1.00 14.67 8 ATOM 1486 N GLY A 328 21.937 25.717 123.002 1.00 14.86 7 ATOM 1487 CA GLY A 328 21.974 27.167 123.138 1.00 14.31 6 ATOM 1488 C GLY A 328 23.362 27.781 123.117 1.00 13.29 6 ATOM 1489 O GLY A 328 24.359 27.093 122.858 1.00 13.38 8 ATOM 1490 N ARG A 329 23.417 29.079 123.425 1.00 13.22 7 ATOM 1491 CA ARG A 329 24.651 29.875 123.434 1.00 11.72 6 ATOM 1492 CB ARG A 329 24.318 31.372 123.559 1.00 13.53 6 ATOM 1493 CG ARG A 329 23.630 31.797 124.846 1.00 14.82 6 ATOM 1494 CD ARG A 329 23.310 33.279 124.808 1.00 17.68 6 ATOM 1495 NE ARG A 329 22.540 33.703 125.977 1.00 21.99 7 ATOM 1496 CZ ARG A 329 22.103 34.945 126.185 1.00 23.44 6 ATOM 1497 NH1 ARG A 329 22.357 35.909 125.308 1.00 25.85 7 ATOM 1498 NH2 ARG A 329 21.399 35.220 127.274 1.00 26.44 7 ATOM 1499 C ARG A 329 25.725 29.498 124.452 1.00 11.40 6 ATOM 1500 O ARG A 329 26.879 29.926 124.326 1.00 11.78 8 ATOM 1501 N ALA A 330 25.347 28.671 125.429 1.00 11.45 7 ATOM 1502 CA ALA A 330 26.247 28.217 126.488 1.00 10.54 6 ATOM 1503 CB ALA A 330 25.475 27.455 127.544 1.00 11.82 6 ATOM 1504 C ALA A 330 27.430 27.385 125.994 1.00 10.14 6 ATOM 1505 O ALA A 330 28.383 27.160 126.742 1.00 8.60 8 ATOM 1506 N VAL A 331 27.384 26.970 124.724 1.00 9.12 7 ATOM 1507 CA VAL A 331 28.472 26.191 124.118 1.00 8.63 6 ATOM 1508 CB VAL A 331 28.113 25.660 122.698 1.00 11.11 6 ATOM 1509 CG1 VAL A 331 26.959 24.696 122.803 1.00 12.10 6 ATOM 1510 CG2 VAL A 331 27.758 26.804 121.731 1.00 12.52 6 ATOM 1511 C VAL A 331 29.778 26.997 124.064 1.00 9.23 6 ATOM 1512 O VAL A 331 30.863 26.427 124.168 1.00 10.98 8 ATOM 1513 N ASP A 332 29.655 28.325 123.984 1.00 9.32 7 ATOM 1514 CA ASP A 332 30.824 29.209 123.945 1.00 8.91 6 ATOM 1515 CB ASP A 332 30.443 30.629 123.504 1.00 8.88 6 ATOM 1516 CG ASP A 332 30.162 30.736 122.011 1.00 10.62 6 ATOM 1517 OD1 ASP A 332 30.610 29.870 121.228 1.00 10.05 8 ATOM 1518 OD2 ASP A 332 29.504 31.721 121.616 1.00 10.52 8 ATOM 1519 C ASP A 332 31.544 29.263 125.292 1.00 9.09 6 ATOM 1520 O ASP A 332 32.770 29.411 125.338 1.00 9.10 8 ATOM 1521 N TRP A 333 30.790 29.065 126.376 1.00 8.71 7 ATOM 1522 CA TRP A 333 31.373 29.084 127.716 1.00 8.19 6 ATOM 1523 CB TRP A 333 30.332 29.445 128.781 1.00 8.93 6 ATOM 1524 CG TRP A 333 29.667 30.777 128.493 1.00 9.61 6 ATOM 1525 CD2 TRP A 333 30.301 32.061 128.340 1.00 9.02 6 ATOM 1526 CE2 TRP A 333 29.287 32.983 127.973 1.00 10.06 6 ATOM 1527 CE3 TRP A 333 31.632 32.527 128.466 1.00 8.81 6 ATOM 1528 CD1 TRP A 333 28.344 30.978 128.234 1.00 11.29 6 ATOM 1529 NE1 TRP A 333 28.106 32.292 127.921 1.00 11.84 7 ATOM 1530 CZ2 TRP A 333 29.556 34.345 127.725 1.00 11.21 6 ATOM 1531 CZ3 TRP A 333 31.903 33.891 128.223 1.00 10.64 6 ATOM 1532 CH2 TRP A 333 30.863 34.780 127.856 1.00 10.80 6 ATOM 1533 C TRP A 333 32.112 27.795 128.015 1.00 9.22 6 ATOM 1534 O TRP A 333 33.123 27.808 128.726 1.00 9.92 8 ATOM 1535 N TRP A 334 31.659 26.705 127.390 1.00 8.46 7 ATOM 1536 CA TRP A 334 32.336 25.414 127.515 1.00 8.84 6 ATOM 1537 CB TRP A 334 31.528 24.292 126.843 1.00 9.12 6 ATOM 1538 CG TRP A 334 32.299 22.992 126.702 1.00 9.84 6 ATOM 1539 CD2 TRP A 334 32.351 21.915 127.642 1.00 9.02 6 ATOM 1540 CE2 TRP A 334 33.249 20.942 127.113 1.00 9.20 6 ATOM 1541 CE3 TRP A 334 31.729 21.667 128.883 1.00 8.01 6 ATOM 1542 CD1 TRP A 334 33.133 22.633 125.666 1.00 9.36 6 ATOM 1543 NE1 TRP A 334 33.704 21.415 125.911 1.00 8.30 7 ATOM 1544 CZ2 TRP A 334 33.548 19.736 127.786 1.00 9.81 6 ATOM 1545 CZ3 TRP A 334 32.027 20.448 129.562 1.00 9.26 6 ATOM 1546 CH2 TRP A 334 32.931 19.507 129.004 1.00 9.81 6 ATOM 1547 C TRP A 334 33.688 25.584 126.804 1.00 8.36 6 ATOM 1548 O TRP A 334 34.724 25.173 127.333 1.00 8.97 8 ATOM 1549 N GLY A 335 33.639 26.146 125.588 1.00 9.05 7 ATOM 1550 CA GLY A 335 34.836 26.390 124.791 1.00 8.76 6 ATOM 1551 C GLY A 335 35.857 27.217 125.548 1.00 9.27 6 ATOM 1552 O GLY A 335 37.054 26.901 125.536 1.00 9.78 8 ATOM 1553 N LEU A 336 35.375 28.255 126.242 1.00 9.15 7 ATOM 1554 CA LEU A 336 36.232 29.115 127.061 1.00 6.99 6 ATOM 1555 CB LEU A 336 35.446 30.288 127.658 1.00 9.20 6 ATOM 1556 CG LEU A 336 36.185 31.146 128.702 1.00 9.11 6 ATOM 1557 CD1 LEU A 336 37.346 31.915 128.075 1.00 10.00 6 ATOM 1558 CD2 LEU A 336 35.218 32.070 129.388 1.00 11.20 6 ATOM 1559 C LEU A 336 36.856 28.274 128.175 1.00 8.42 6 ATOM 1560 O LEU A 336 38.040 28.422 128.476 1.00 8.70 8 ATOM 1561 N GLY A 337 36.060 27.359 128.730 1.00 8.61 7 ATOM 1562 CA GLY A 337 36.533 26.470 129.781 1.00 9.31 6 ATOM 1563 C GLY A 337 37.658 25.562 129.338 1.00 9.78 6 ATOM 1564 O GLY A 337 38.616 25.361 130.081 1.00 9.12 8 ATOM 1565 N VAL A 338 37.557 25.053 128.109 1.00 7.99 7 ATOM 1566 CA VAL A 338 38.588 24.173 127.554 1.00 8.61 6 ATOM 1567 CB VAL A 338 38.132 23.492 126.245 1.00 7.04 6 ATOM 1568 CG1 VAL A 338 39.176 22.505 125.766 1.00 7.76 6 ATOM 1569 CG2 VAL A 338 36.828 22.739 126.451 1.00 9.22 6 ATOM 1570 C VAL A 338 39.896 24.954 127.345 1.00 7.70 6 ATOM 1571 O VAL A 338 40.953 24.480 127.763 1.00 8.42 8 ATOM 1572 N VAL A 339 39.821 26.168 126.784 1.00 9.32 7 ATOM 1573 CA VAL A 339 41.044 26.967 126.589 1.00 8.89 6 ATOM 1574 CB VAL A 339 40.910 28.158 125.580 1.00 11.16 6 ATOM 1575 CG1 VAL A 339 40.548 27.642 124.216 1.00 9.52 6 ATOM 1576 CG2 VAL A 339 39.928 29.205 126.035 1.00 14.02 6 ATOM 1577 C VAL A 339 41.657 27.434 127.908 1.00 8.65 6 ATOM 1578 O VAL A 339 42.874 27.454 128.030 1.00 8.94 8 ATOM 1579 N MET A 340 40.817 27.743 128.904 1.00 9.44 7 ATOM 1580 CA MET A 340 41.307 28.162 130.224 1.00 8.92 6 ATOM 1581 CB MET A 340 40.177 28.715 131.098 1.00 11.70 6 ATOM 1582 CG MET A 340 39.645 30.076 130.689 1.00 13.05 6 ATOM 1583 SD MET A 340 40.858 31.386 130.694 1.00 15.73 16 ATOM 1584 CE MET A 340 40.961 31.748 132.409 1.00 15.84 6 ATOM 1585 C MET A 340 41.978 26.977 130.924 1.00 8.24 6 ATOM 1586 O MET A 340 42.997 27.147 131.606 1.00 8.98 8 ATOM 1587 N TYR A 341 41.437 25.775 130.696 1.00 8.73 7 ATOM 1588 CA TYR A 341 41.990 24.540 131.264 1.00 8.30 6 ATOM 1589 CB TYR A 341 41.048 23.338 131.025 1.00 8.53 6 ATOM 1590 CG TYR A 341 41.451 22.067 131.758 1.00 9.94 6 ATOM 1591 CD1 TYR A 341 42.493 21.251 131.269 1.00 9.71 6 ATOM 1592 CE1 TYR A 341 42.930 20.119 131.967 1.00 9.21 6 ATOM 1593 CD2 TYR A 341 40.840 21.703 132.976 1.00 9.17 6 ATOM 1594 CE2 TYR A 341 41.279 20.549 133.695 1.00 10.70 6 ATOM 1595 CZ TYR A 341 42.326 19.776 133.171 1.00 10.86 6 ATOM 1596 OH TYR A 341 42.788 18.671 133.824 1.00 13.11 8 ATOM 1597 C TYR A 341 43.354 24.298 130.625 1.00 8.67 6 ATOM 1598 O TYR A 341 44.320 23.996 131.324 1.00 9.19 8 ATOM 1599 N GLU A 342 43.428 24.433 129.301 1.00 7.61 7 ATOM 1600 CA GLU A 342 44.690 24.241 128.587 1.00 7.62 6 ATOM 1601 CB GLU A 342 44.490 24.394 127.091 1.00 6.73 6 ATOM 1602 CG GLU A 342 43.754 23.252 126.454 1.00 8.69 6 ATOM 1603 CD GLU A 342 43.578 23.471 124.987 1.00 9.65 6 ATOM 1604 OE1 GLU A 342 42.683 24.256 124.622 1.00 10.41 8 ATOM 1605 OE2 GLU A 342 44.349 22.881 124.197 1.00 10.20 8 ATOM 1606 C GLU A 342 45.760 25.223 129.044 1.00 9.35 6 ATOM 1607 O GLU A 342 46.914 24.843 129.226 1.00 9.34 8 ATOM 1608 N MET A 343 45.358 26.475 129.259 1.00 9.44 7 ATOM 1609 CA MET A 343 46.286 27.514 129.696 1.00 9.68 6 ATOM 1610 CD MET A 343 45.656 28.901 129.566 1.00 9.67 6 ATOM 1611 CG MET A 343 45.457 29.356 128.134 1.00 10.76 6 ATOM 1612 SD MET A 343 45.043 31.114 128.013 1.00 12.47 16 ATOM 1613 CE MET A 343 43.291 31.044 128.001 1.00 16.49 6 ATOM 1614 C MET A 343 46.812 27.325 131.115 1.00 11.09 6 ATOM 1615 O MET A 343 47.980 27.587 131.377 1.00 12.53 8 ATOM 1616 N MET A 344 45.960 26.829 132.013 1.00 9.99 7 ATOM 1617 CA MET A 344 46.361 26.644 133.408 1.00 10.38 6 ATOM 1618 CB MET A 344 45.266 27.135 134.358 1.00 11.17 6 ATOM 1619 CG MET A 344 45.012 28.613 134.232 1.00 13.27 6 ATOM 1620 SD MET A 344 43.867 29.333 135.412 1.00 13.11 16 ATOM 1621 CE MET A 344 42.327 28.674 134.857 1.00 13.34 6 ATOM 1622 C MET A 344 46.820 25.251 133.815 1.00 10.46 6 ATOM 1623 O MET A 344 47.549 25.110 134.804 1.00 11.06 8 ATOM 1624 N CYS A 345 46.436 24.234 133.046 1.00 11.99 7 ATOM 1625 CA CYS A 345 46.818 22.858 133.369 1.00 11.03 6 ATOM 1626 CB CYS A 345 45.576 21.998 133.584 1.00 10.84 6 ATOM 1627 SG CYS A 345 44.373 22.685 134.751 1.00 13.23 16 ATOM 1628 C CYS A 345 47.767 22.190 132.373 1.00 11.63 6 ATOM 1629 O CYS A 345 48.205 21.059 132.598 1.00 14.38 8 ATOM 1630 N GLY A 346 48.065 22.875 131.268 1.00 11.83 7 ATOM 1631 CA GLY A 346 48.998 22.352 130.278 1.00 12.50 6 ATOM 1632 C GLY A 346 48.575 21.212 129.368 1.00 12.69 6 ATOM 1633 O GLY A 346 49.428 20.592 128.729 1.00 15.89 8 ATOM 1634 N ARG A 347 47.276 20.920 129.324 1.00 11.55 7 ATOM 1635 CA ARG A 347 46.727 19.860 128.472 1.00 11.09 6 ATOM 1636 CB ARG A 347 46.959 18.458 129.084 1.00 10.99 6 ATOM 1637 CC ARG A 347 46.334 18.210 130.471 1.00 13.53 6 ATOM 1638 CD ARG A 347 46.271 16.716 130.754 1.00 13.47 6 ATOM 1639 NE ARG A 347 45.685 16.370 132.050 1.00 14.43 7 ATOM 1640 CZ ARG A 347 44.397 16.097 132.253 1.00 14.07 6 ATOM 1641 NH1 ARG A 347 43.531 16.151 131.250 1.00 13.52 7 ATOM 1642 NH2 ARG A 347 43.990 15.663 133.441 1.00 12.66 7 ATOM 1643 C ARG A 347 45.235 20.073 128.297 1.00 11.67 6 ATOM 1644 O ARG A 347 44.637 20.876 129.008 1.00 10.21 8 ATOM 1645 N LEU A 348 44.645 19.346 127.348 1.00 11.53 7 ATOM 1646 CA LEU A 348 43.201 19.374 127.111 1.00 10.75 6 ATOM 1647 CB LEU A 348 42.860 18.654 125.800 1.00 11.50 6 ATOM 1648 CG LEU A 348 42.983 19.406 124.478 1.00 8.45 6 ATOM 1649 CD1 LUE A 348 42.936 18.422 123.336 1.00 11.45 6 ATOM 1650 CD2 LEU A 348 41.860 20.408 124.327 1.00 10.40 6 ATOM 1651 C LEU A 348 42.561 18.599 128.268 1.00 10.74 6 ATOM 1652 O LEU A 348 43.202 17.706 128.834 1.00 10.76 8 ATOM 1653 N PRO A 349 41.328 18.966 128.681 1.00 9.41 7 ATOM 1654 CD PRO A 349 40.521 20.142 128.299 1.00 10.39 6 ATOM 1655 CA PRO A 349 40.680 18.237 129.779 1.00 10.53 6 ATOM 1656 CB PRO A 349 39.440 19.086 130.071 1.00 10.90 6 ATOM 1657 CG PRO A 349 39.156 19.764 128.779 1.00 10.53 6 ATOM 1658 C PRO A 349 40.349 16.791 129.419 1.00 11.31 6 ATOM 1659 O PRO A 349 40.373 15.906 130.283 1.00 13.75 8 ATOM 1660 N PHE A 350 40.078 16.570 128.132 1.00 12.53 7 ATOM 1661 CA PHE A 350 39.746 15.250 127.586 1.00 13.42 6 ATOM 1662 CB PHE A 350 38.241 15.128 127.292 1.00 14.48 6 ATOM 1663 CG PHE A 350 37.355 15.549 128.424 1.00 14.54 6 ATOM 1664 CD1 PHE A 350 37.234 14.752 129.576 1.00 16.30 6 ATOM 1665 CD2 PHE A 350 36.662 16.774 128.360 1.00 15.73 6 ATOM 1666 CE1 PHE A 350 36.431 15.171 130.664 1.00 18.06 6 ATOM 1667 CE2 PHE A 350 35.857 17.208 129.437 1.00 15.86 6 ATOM 1668 CZ PHE A 350 35.741 16.405 130.591 1.00 16.17 6 ATOM 1669 C PHE A 350 40.471 15.060 126.267 1.00 12.83 6 ATOM 1670 O PHE A 350 40.428 15.944 125.403 1.00 13.29 8 ATOM 1671 N TYR A 351 41.135 13.913 126.105 1.00 12.93 7 ATOM 1672 CA TYR A 351 41.825 13.614 124.852 1.00 12.91 6 ATOM 1673 CB TYR A 351 43.209 14.309 124.749 1.00 13.23 6 ATOM 1674 CG TYR A 351 43.842 14.174 123.364 1.00 13.94 6 ATOM 1675 CD1 TYR A 351 43.268 14.814 122.242 1.00 14.53 6 ATOM 1676 CE1 TYR A 351 43.752 14.576 120.925 1.00 16.62 6 ATOM 1677 CD2 TYR A 351 44.932 13.296 123.144 1.00 15.83 6 ATOM 1678 CE2 TYR A 351 45.423 13.047 121.829 1.00 16.82 6 ATOM 1679 CZ TYR A 351 44.824 13.689 120.733 1.00 18.28 6 ATOM 1680 OH TYR A 351 45.272 13.435 119.459 1.00 19.92 8 ATOM 1681 C TYR A 351 41.985 12.133 124.523 1.00 14.39 6 ATOM 1682 O TYR A 351 42.246 11.308 125.393 1.00 15.38 8 ATOM 1683 N ASN A 352 41.842 11.858 123.226 1.00 17.37 7 ATOM 1684 CA ASN A 352 42.026 10.555 122.593 1.00 17.46 6 ATOM 1685 CB ASN A 352 40.901 9.566 122.925 1.00 17.47 6 ATOM 1686 CG ASN A 352 41.277 8.125 122.589 1.00 18.57 6 ATOM 1687 OD1 ASN A 352 41.439 7.767 121.419 1.00 18.31 8 ATOM 1688 ND2 ASN A 352 41.386 7.292 123.611 1.00 17.26 7 ATOM 1689 C ASN A 352 42.064 10.842 121.089 1.00 18.31 6 ATOM 1690 O ASN A 352 41.280 11.658 120.591 1.00 17.49 8 ATOM 1691 N GLN A 353 42.978 10.174 120.379 1.00 19.27 7 ATOM 1692 CA GLN A 353 43.149 10.338 118.925 1.00 21.81 6 ATOM 1693 CB GLN A 353 44.433 9.637 118.440 1.00 24.32 6 ATOM 1694 CG GLN A 353 44.594 8.157 118.836 1.00 30.30 6 ATOM 1695 CD GLN A 353 44.335 7.188 117.691 1.00 33.66 6 ATOM 1696 OE1 GLN A 353 44.976 7.261 116.640 1.00 37.01 8 ATOM 1697 NE2 GLN A 353 43.402 6.265 117.898 1.00 33.69 7 ATOM 1698 C GLN A 353 41.942 9.889 118.097 1.00 21.52 6 ATOM 1699 O GLN A 353 41.704 10.401 117.000 1.00 21.80 8 ATOM 1700 N ASP A 354 41.191 8.937 118.647 1.00 21.45 7 ATOM 1701 CA ASP A 354 39.991 8.404 118.012 1.00 22.73 6 ATOM 1702 CB ASP A 354 39.813 6.928 118.394 1.00 26.02 6 ATOM 1703 CG ASP A 354 38.641 6.271 117.686 1.00 29.87 6 ATOM 1704 OD1 ASP A 354 37.604 6.066 118.345 1.00 31.99 8 ATOM 1705 OD2 ASP A 354 38.758 5.969 116.478 1.00 33.29 8 ATOM 1706 C ASP A 354 38.808 9.244 118.497 1.00 21.80 6 ATOM 1707 O ASP A 354 38.584 9.364 119.708 1.00 20.12 8 ATOM 1708 N HIS A 355 38.067 9.815 117.545 1.00 21.41 7 ATOM 1709 CA HIS A 355 36.905 10.666 117.826 1.00 20.97 6 ATOM 1710 CB HIS A 355 36.333 11.261 116.535 1.00 21.55 6 ATOM 1711 CG HIS A 355 37.187 12.329 115.916 1.00 22.01 6 ATOM 1712 CD2 HIS A 355 38.287 12.980 116.369 1.00 21.34 6 ATOM 1713 ND1 HIS A 355 36.930 12.845 114.664 1.00 22.26 7 ATOM 1714 CE1 HIS A 355 37.833 13.763 114.372 1.00 21.26 6 ATOM 1715 NE2 HIS A 355 38.668 13.865 115.391 1.00 21.37 7 ATOM 1716 C HIS A 355 35.789 10.015 118.635 1.00 21.47 6 ATOM 1717 O HIS A 355 35.186 10.672 119.478 1.00 19.43 8 ATOM 1718 N GLU A 356 35.556 8.718 118.419 1.00 21.21 7 ATOM 1719 CA GLU A 356 34.519 7.980 119.148 1.00 22.54 6 ATOM 1720 CB GLU A 356 34.336 6.568 118.578 1.00 26.75 6 ATOM 1721 CG GLU A 356 33.796 6.522 117.155 1.00 32.55 6 ATOM 1722 CD GLU A 356 33.523 5.104 116.682 1.00 35.70 6 ATOM 1723 OE1 GLU A 356 34.381 4.536 115.972 1.00 38.74 8 ATOM 1724 OE2 GLU A 356 32.450 4.558 117.020 1.00 38.53 8 ATOM 1725 C GLU A 356 34.838 7.901 120.640 1.00 21.22 6 ATOM 1726 O GLU A 356 33.967 8.145 121.474 1.00 20.29 8 ATOM 1727 N ARG A 357 36.108 7.641 120.962 1.00 17.62 7 ATOM 1728 CA ARG A 357 36.560 7.551 122.352 1.00 17.27 6 ATOM 1729 CB ARG A 357 37.940 6.895 122.440 1.00 18.72 6 ATOM 1730 CG ARG A 357 38.081 5.493 121.837 1.00 21.62 6 ATOM 1731 CD ARG A 357 37.375 4.398 122.649 1.00 25.76 6 ATOM 1732 NE ARG A 357 35.952 4.261 122.321 1.00 28.83 7 ATOM 1733 CZ ARG A 357 35.469 3.642 121.243 1.00 31.00 6 ATOM 1734 NH1 ARG A 357 34.158 3.585 121.053 1.00 32.78 7 ATOM 1735 NH2 ARG A 357 36.283 3.084 120.351 1.00 31.71 7 ATOM 1736 C ARG A 357 36.604 8.939 122.997 1.00 14.83 6 ATOM 1737 O ARG A 357 36.263 9.089 124.168 1.00 15.40 8 ATOM 1738 N LEU A 358 36.979 9.947 122.205 1.00 14.70 7 ATOM 1739 CA LEU A 358 37.051 11.344 122.656 1.00 12.81 6 ATOM 1740 CB LEU A 358 37.616 12.230 121.536 1.00 11.65 6 ATOM 1741 CG LEU A 358 37.579 13.762 121.633 1.00 13.52 6 ATOM 1742 CD1 LEU A 358 38.508 14.283 122.724 1.00 12.41 6 ATOM 1743 CD2 LEU A 358 37.951 14.336 120.288 1.00 14.63 6 ATOM 1744 C LEU A 358 35.664 11.855 123.071 1.00 12.62 6 ATOM 1745 O LEU A 358 35.517 12.476 124.126 1.00 11.73 8 ATOM 1746 N PHE A 359 34.659 11.544 122.254 1.00 13.10 7 ATOM 1747 CA PHE A 359 33.275 11.958 122.510 1.00 12.39 6 ATOM 1748 CB PHE A 359 32.388 11.681 121.289 1.00 13.62 6 ATOM 1749 CG PHE A 359 32.752 12.492 120.060 1.00 13.81 6 ATOM 1750 CD1 PHE A 359 32.260 12.109 118.799 1.00 17.10 6 ATOM 1751 CD2 PHE A 359 33.574 13.645 120.146 1.00 14.48 6 ATOM 1752 CE1 PHE A 359 32.575 12.857 117.631 1.00 16.66 6 ATOM 1753 CE2 PHE A 359 33.900 14.405 118.989 1.00 14.90 6 ATOM 1754 CZ PHE A 359 33.397 14.009 117.728 1.00 17.66 6 ATOM 1755 C PHE A 359 32.696 11.322 123.764 1.00 12.91 6 ATOM 1756 O PHE A 359 31.934 11.961 124.490 1.00 12.60 8 ATOM 1757 N GLU A 360 33.121 10.088 124.043 1.00 13.55 7 ATOM 1758 CA GLU A 360 32.704 9.364 125.241 1.00 13.47 6 ATOM 1759 CB GLU A 360 33.149 7.901 125.180 1.00 16.22 6 ATOM 1760 CG GLU A 360 32.388 7.048 124.170 1.00 20.13 6 ATOM 1761 CD GLU A 360 33.052 5.701 123.883 1.00 24.13 6 ATOM 1762 OE1 GLU A 360 34.175 5.446 124.376 1.00 25.34 8 ATOM 1763 OE2 GLU A 360 32.446 4.896 123.142 1.00 26.73 8 ATOM 1764 C GLU A 360 33.315 10.043 126.468 1.00 12.66 6 ATOM 1765 O GLU A 360 32.655 10.174 127.488 1.00 13.30 8 ATOM 1766 N LEU A 361 34.552 10.533 126.341 1.00 12.65 7 ATOM 1767 CA LEU A 361 35.223 11.224 127.449 1.00 11.47 6 ATOM 1768 CB LEU A 361 36.703 11.464 127.139 1.00 12.45 6 ATOM 1769 CG LEU A 361 37.648 10.264 127.039 1.00 14.17 6 ATOM 1770 CD1 LEU A 361 38.996 10.757 126.560 1.00 17.03 6 ATOM 1771 CD2 LEU A 361 37.779 9.541 128.371 1.00 15.99 6 ATOM 1772 C LEU A 361 34.538 12.552 127.770 1.00 11.43 6 ATOM 1773 O LEU A 361 34.242 12.839 128.931 1.00 11.50 8 ATOM 1774 N ILE A 362 34.219 13.318 126.725 1.00 11.48 7 ATOM 1775 CA ILE A 362 33.545 14.612 126.877 1.00 10.21 6 ATOM 1776 CB ILE A 362 33.421 15.345 125.499 1.00 9.29 6 ATOM 1777 CG2 ILE A 362 32.533 16.599 125.610 1.00 10.17 6 ATOM 1778 CG1 ILE A 362 34.811 15.744 124.989 1.00 9.91 6 ATOM 1779 CD1 ILE A 362 34.834 16.247 123.541 1.00 9.88 6 ATOM 1780 C ILE A 362 32.170 14.442 127.554 1.00 11.21 6 ATOM 1781 O ILE A 362 31.819 15.214 128.443 1.00 11.78 8 ATOM 1782 N LEU A 363 31.456 13.379 127.191 1.00 12.20 7 ATOM 1783 CA LEU A 363 30.137 13.109 127.758 1.00 12.73 6 ATOM 1784 CB LEU A 363 29.300 12.258 126.794 1.00 14.32 6 ATOM 1785 CG LEU A 363 28.665 12.880 125.550 1.00 14.53 6 ATOM 1786 CD1 LEU A 363 28.325 11.777 124.567 1.00 14.87 6 ATOM 1787 CD2 LEU A 363 27.426 13.687 125.909 1.00 14.45 6 ATOM 1788 C LEU A 363 30.122 12.424 129.117 1.00 12.93 6 ATOM 1789 O LEU A 363 29.303 12.779 129.960 1.00 13.39 8 ATOM 1790 N MET A 364 31.061 11.498 129.339 1.00 14.47 7 ATOM 1791 CA MET A 364 31.102 10.678 130.566 1.00 16.00 6 ATOM 1792 CB MET A 364 31.163 9.180 130.202 1.00 18.46 6 ATOM 1793 CG MET A 364 30.356 8.707 129.005 1.00 23.38 6 ATOM 1794 SD MET A 364 28.613 8.855 129.251 1.00 24.01 16 ATOM 1795 CE MET A 364 28.003 8.551 127.568 1.00 24.53 6 ATOM 1796 C MET A 364 32.188 10.886 131.620 1.00 15.59 6 ATOM 1797 O MET A 364 31.963 10.582 132.793 1.00 16.28 8 ATOM 1798 N GLU A 365 33.378 11.321 131.208 1.00 14.43 7 ATOM 1799 CA GLU A 365 34.498 11.479 132.145 1.00 16.41 6 ATOM 1800 CB GLU A 365 35.835 11.325 131.399 1.00 16.07 6 ATOM 1801 CG GLU A 365 37.082 11.102 132.268 1.00 19.18 6 ATOM 1802 CD GLU A 365 37.026 9.816 133.067 1.00 21.17 6 ATOM 1803 OE1 GLU A 365 37.349 8.750 132.503 1.00 26.02 8 ATOM 1804 OE2 GLU A 365 36.656 9.877 134.258 1.00 21.86 8 ATOM 1805 C GLU A 365 34.499 12.761 132.962 1.00 16.84 6 ATOM 1806 O GLU A 365 34.123 13.818 132.470 1.00 16.32 8 ATOM 1807 N GLU A 366 34.908 12.650 134.223 1.00 17.73 7 ATOM 1808 CA GLU A 366 34.987 13.817 135.086 1.00 19.92 6 ATOM 1809 CB GLU A 366 34.583 13.499 136.532 1.00 24.89 6 ATOM 1810 CG GLU A 366 35.166 12.236 137.140 1.00 30.53 6 ATOM 1811 CD GLU A 366 34.581 11.947 138.515 1.00 33.80 6 ATOM 1812 OE1 GLU A 366 33.577 11.203 138.597 1.00 36.28 8 ATOM 1813 OE2 GLU A 366 35.118 12.477 139.511 1.00 37.13 8 ATOM 1814 C GLU A 366 36.376 14.437 135.001 1.00 18.55 6 ATOM 1815 O GLU A 366 37.382 13.726 134.861 1.00 17.68 8 ATOM 1816 N ILE A 367 36.416 15.811 134.833 1.00 18.45 7 ATOM 1817 CA ILE A 367 37.652 16.582 134.699 1.00 17.54 6 ATOM 1818 CB ILE A 367 37.394 18.061 134.286 1.00 19.96 6 ATOM 1819 CG2 ILE A 367 36.716 18.114 132.934 1.00 21.02 6 ATOM 1820 CG1 ILE A 367 36.628 18.809 135.385 1.00 22.52 6 ATOM 1821 CD1 ILE A 367 36.540 20.305 135.191 1.00 27.16 6 ATOM 1822 C ILE A 367 38.483 16.598 135.968 1.00 15.97 6 ATOM 1823 O ILE A 367 37.955 16.534 137.082 1.00 15.78 8 ATOM 1824 N ARG A 368 39.803 16.437 135.955 1.00 15.49 7 ATOM 1825 CA ARG A 368 40.750 16.373 137.054 1.00 13.91 6 ATOM 1826 CB ARG A 368 41.701 15.190 136.884 1.00 16.07 6 ATOM 1827 CG ARG A 368 40.996 13.853 137.023 1.00 16.26 6 ATOM 1828 CD ARG A 368 41.915 12.688 136.772 1.00 18.15 6 ATOM 1829 NE ARG A 368 42.957 12.546 137.789 1.00 16.36 7 ATOM 1830 CZ ARG A 368 42.801 11.937 138.964 1.00 15.91 6 ATOM 1831 NH1 ARG A 368 41.630 11.411 139.307 1.00 13.91 7 ATOM 1832 NH2 ARG A 368 43.844 11.788 139.771 1.00 15.42 7 ATOM 1833 C ARG A 368 41.506 17.686 137.108 1.00 14.00 6 ATOM 1834 O ARG A 368 41.591 18.396 136.107 1.00 13.74 8 ATOM 1835 N PHE A 369 41.999 18.036 138.292 1.00 12.44 7 ATOM 1836 CA PHE A 369 42.733 19.281 138.483 1.00 13.72 6 ATOM 1837 CB PHE A 369 41.942 20.260 139.374 1.00 16.01 6 ATOM 1838 CG PHE A 369 40.580 20.606 138.865 1.00 19.40 6 ATOM 1839 CD1 PHE A 369 40.422 21.319 137.663 1.00 21.31 6 ATOM 1840 CD2 PHE A 369 39.441 20.234 139.600 1.00 21.41 6 ATOM 1841 CE1 PHE A 369 39.134 21.660 137.194 1.00 22.27 6 ATOM 1842 CE2 PHE A 369 38.143 20.569 139.147 1.00 22.48 6 ATOM 1843 CZ PHE A 369 37.993 21.285 137.939 1.00 22.67 6 ATOM 1844 C PHE A 369 44.048 19.051 139.202 1.00 12.99 6 ATOM 1845 O PHE A 369 44.107 18.221 140.116 1.00 13.28 8 ATOM 1846 N PRO A 370 45.122 19.791 138.821 1.00 12.62 7 ATOM 1847 CD PRO A 370 45.265 20.647 137.623 1.00 12.97 6 ATOM 1848 CA PRO A 370 46.422 19.644 139.495 1.00 13.27 6 ATOM 1849 CB PRO A 370 47.305 20.640 138.743 1.00 13.28 6 ATOM 1850 CG PRO A 370 46.742 20.610 137.366 1.00 12.02 6 ATOM 1851 C PRO A 370 46.192 20.106 140.947 1.00 14.38 6 ATOM 1852 O PRO A 370 45.426 21.048 141.170 1.00 13.19 8 ATOM 1853 N ARG A 371 46.769 19.401 141.922 1.00 14.63 7 ATOM 1854 CA ARG A 371 46.597 19.738 143.348 1.00 14.85 6 ATOM 1855 CB ARG A 371 47.450 18.820 144.224 1.00 15.50 6 ATOM 1856 CG ARG A 371 46.972 17.397 144.280 1.00 15.64 6 ATOM 1857 CD ARG A 371 47.941 16.522 145.048 1.00 16.52 6 ATOM 1858 NE ARG A 371 47.656 15.103 144.849 1.00 16.74 7 ATOM 1859 CZ ARG A 371 46.781 14.386 145.555 1.00 19.95 6 ATOM 1860 NH1 ARG A 371 46.076 14.937 146.536 1.00 20.23 7 ATOM 1861 NH2 ARG A 371 46.638 13.092 145.295 1.00 20.68 7 ATOM 1862 C ARG A 371 46.916 21.184 143.719 1.00 16.34 6 ATOM 1863 O ARG A 371 46.215 21.795 144.534 1.00 18.32 8 ATOM 1864 N THR A 372 47.919 21.730 143.034 1.00 16.70 7 ATOM 1865 CA THR A 372 48.428 23.082 143.242 1.00 16.75 6 ATOM 1866 CB THR A 372 49.875 23.187 142.733 1.00 17.33 6 ATOM 1867 OG1 THR A 372 49.920 22.801 141.353 1.00 19.65 8 ATOM 1868 CG2 THR A 372 50.792 22.285 143.548 1.00 18.72 6 ATOM 1869 C THR A 372 47.629 24.229 142.631 1.00 16.67 6 ATOM 1870 O THR A 372 47.926 25.397 142.896 1.00 18.53 8 ATOM 1871 N LEU A 373 46.634 23.902 141.806 1.00 15.88 7 ATOM 1872 CA LEU A 373 45.789 24.914 141.170 1.00 15.90 6 ATOM 1873 CB LEU A 373 44.868 24.252 140.138 1.00 15.93 6 ATOM 1874 CG LEU A 373 44.191 25.081 139.043 1.00 17.27 6 ATOM 1875 CD1 LEU A 373 45.215 25.763 138.140 1.00 16.45 6 ATOM 1876 CD2 LEU A 373 43.282 24.176 138.225 1.00 16.38 6 ATOM 1877 C LEU A 373 44.983 25.602 142.275 1.00 15.67 6 ATOM 1878 O LEU A 373 44.515 24.943 143.203 1.00 16.32 8 ATOM 1879 N SER A 374 44.893 26.930 142.210 1.00 16.49 7 ATOM 1880 CA SER A 374 44.173 27.721 143.215 1.00 15.44 6 ATOM 1881 CB SER A 374 44.305 29.214 142.897 1.00 15.83 6 ATOM 1882 OG SER A 374 43.444 29.598 141.832 1.00 15.83 8 ATOM 1883 C SER A 374 42.690 27.331 143.310 1.00 15.40 6 ATOM 1884 O SER A 374 42.124 26.842 142.323 1.00 13.74 8 ATOM 1885 N PRO A 375 42.059 27.483 144.502 1.00 14.76 7 ATOM 1886 CD PRO A 375 42.604 27.786 145.841 1.00 17.28 6 ATOM 1887 CA PRO A 375 40.638 27.120 144.609 1.00 15.31 6 ATOM 1888 CB PRO A 375 40.321 27.359 146.092 1.00 17.41 6 ATOM 1889 CG PRO A 375 41.396 28.301 146.554 1.00 19.00 6 ATOM 1890 C PRO A 375 39.711 27.904 143.671 1.00 13.52 6 ATOM 1891 O PRO A 375 38.742 27.343 143.160 1.00 14.01 8 ATOM 1892 N GLU A 376 40.071 29.157 143.378 1.00 13.97 7 ATOM 1893 CA GLU A 376 39.275 29.998 142.475 1.00 14.68 6 ATOM 1894 CB GLU A 376 39.629 31.491 142.625 1.00 16.36 6 ATOM 1895 CG GLU A 376 41.058 31.913 142.261 1.00 18.50 6 ATOM 1896 CD GLU A 376 42.012 31.990 143.446 1.00 21.12 6 ATOM 1897 OE1 GLU A 376 41.779 31.324 144.484 1.00 21.38 8 ATOM 1898 OE2 GLU A 376 43.031 32.701 143.313 1.00 21.74 8 ATOM 1899 C GLU A 376 39.388 29.539 141.015 1.00 12.95 6 ATOM 1900 O GLU A 376 38.422 29.645 140.256 1.00 12.83 8 ATOM 1901 N ALA A 377 40.548 28.981 140.653 1.00 13.12 7 ATOM 1902 CA ALA A 377 40.774 28.464 139.298 1.00 11.85 6 ATOM 1903 CB ALA A 377 42.257 28.341 139.001 1.00 12.26 6 ATOM 1904 C ALA A 377 40.064 27.125 139.133 1.00 11.84 6 ATOM 1905 O ALA A 377 39.432 26.886 138.103 1.00 9.99 8 ATOM 1906 N LYS A 378 40.092 26.297 140.183 1.00 11.84 7 ATOM 1907 CA LYS A 378 39.410 24.995 140.183 1.00 13.06 6 ATOM 1908 CB LYS A 378 39.704 24.213 141.468 1.00 14.52 6 ATOM 1909 CG LYS A 378 41.101 23.644 141.556 1.00 17.99 6 ATOM 1910 CD LYS A 378 41.306 22.873 142.855 1.00 19.65 6 ATOM 1911 CE LYS A 378 42.704 22.287 142.922 1.00 21.10 6 ATOM 1912 NZ LYS A 378 42.977 21.595 144.209 1.00 22.29 7 ATOM 1913 C LYS A 378 37.899 25.205 140.057 1.00 13.94 6 ATOM 1914 O LYS A 378 37.229 24.487 139.315 1.00 14.33 8 ATOM 1915 N SER A 379 37.401 26.243 140.734 1.00 14.15 7 ATOM 1916 CA SER A 379 35.982 26.607 140.723 1.00 13.37 6 ATOM 1917 CB SER A 379 35.685 27.639 141.814 1.00 15.19 6 ATOM 1918 OG SER A 379 34.330 28.054 141.773 1.00 15.89 8 ATOM 1919 C SER A 379 35.539 27.138 139.358 1.00 12.93 6 ATOM 1920 O SER A 379 34.451 26.793 138.885 1.00 13.31 8 ATOM 1921 N LEU A 380 36.394 27.945 138.723 1.00 11.53 7 ATOM 1922 CA LEU A 380 36.103 28.502 137.397 1.00 10.62 6 ATOM 1923 CB LEU A 380 37.180 29.503 136.958 1.00 9.63 6 ATOM 1924 CG LEU A 380 36.877 30.166 135.603 1.00 8.61 6 ATOM 1925 CD1 LEU A 380 35.950 31.364 135.781 1.00 11.46 6 ATOM 1926 CD2 LEU A 380 38.151 30.554 134.897 1.00 8.47 6 ATOM 1927 C LEU A 380 36.018 27.389 136.363 1.00 10.95 6 ATOM 1928 O LEU A 380 35.047 27.305 135.614 1.00 11.23 8 ATOM 1929 N LEU A 381 37.034 26.526 136.355 1.00 11.57 7 ATOM 1930 CA LEU A 381 37.086 25.416 135.416 1.00 11.41 6 ATOM 1931 CB LEU A 381 38.453 24.732 135.468 1.00 11.23 6 ATOM 1932 CG LEU A 381 39.645 25.610 135.088 1.00 10.95 6 ATOM 1933 CD1 LEU A 381 40.930 24.817 135.194 1.00 12.71 6 ATOM 1934 CD2 LEU A 381 39.458 26.159 133.687 1.00 12.68 6 ATOM 1935 C LEU A 381 35.954 24.418 135.610 1.00 11.97 6 ATOM 1936 O LEU A 381 35.336 24.017 134.639 1.00 11.66 8 ATOM 1937 N ALA A 382 35.614 24.115 136.866 1.00 12.85 7 ATOM 1938 CA ALA A 382 34.514 23.192 137.182 1.00 13.62 6 ATOM 1939 CB ALA A 382 34.486 22.889 138.674 1.00 13.28 6 ATOM 1940 C ALA A 382 33.178 23.794 136.740 1.00 12.66 6 ATOM 1941 O ALA A 382 32.294 23.086 136.256 1.00 13.18 8 ATOM 1942 N GLY A 383 33.092 25.122 136.841 1.00 12.74 7 ATOM 1943 CA GLY A 383 31.895 25.850 136.454 1.00 11.76 6 ATOM 1944 C GLY A 383 31.718 25.948 134.950 1.00 11.24 6 ATOM 1945 O GLY A 383 30.631 25.680 134.436 1.00 12.23 8 ATOM 1946 N LEU A 384 32.789 26.316 134.242 1.00 10.28 7 ATOM 1947 CA LEU A 384 32.750 26.447 132.785 1.00 8.37 6 ATOM 1948 CB LEU A 384 33.974 27.211 132.280 1.00 7.94 6 ATOM 1949 CG LEU A 384 34.093 28.707 132.579 1.00 8.98 6 ATOM 1950 CD1 LEU A 384 35.462 29.193 132.160 1.00 8.46 6 ATOM 1951 CD2 LEU A 384 33.003 29.493 131.861 1.00 8.33 6 ATOM 1952 C LEU A 384 32.657 25.093 132.097 1.00 9.44 6 ATOM 1953 O LEU A 384 32.067 24.973 131.022 1.00 10.70 8 ATOM 1954 N LEU A 385 33.233 24.076 132.737 1.00 9.05 7 ATOM 1955 CA LEU A 385 33.210 22.723 132.205 1.00 8.54 6 ATOM 1956 CB LEU A 385 34.598 22.074 132.241 1.00 8.08 6 ATOM 1957 CG LEU A 385 35.672 22.751 131.388 1.00 9.70 6 ATOM 1958 CD1 LEU A 385 37.020 22.131 131.665 1.00 10.31 6 ATOM 1959 CD2 LEU A 385 35.323 22.662 129.917 1.00 10.87 6 ATOM 1960 C LEU A 385 32.142 21.813 132.815 1.00 9.69 6 ATOM 1961 O LEU A 385 32.278 20.584 132.825 1.00 11.63 8 ATOM 1962 N LYS A 386 31.046 22.422 133.271 1.00 11.61 7 ATOM 1963 CA LYS A 386 29.924 21.660 133.817 1.00 13.81 6 ATOM 1964 CB LYS A 386 28.984 22.571 134.604 1.00 15.59 6 ATOM 1965 CG LYS A 386 28.104 21.864 135.621 1.00 23.17 6 ATOM 1966 CD LYS A 386 28.838 21.600 136.927 1.00 25.66 6 ATOM 1967 CE LYS A 386 27.922 20.942 137.945 1.00 30.60 6 ATOM 1968 NZ LYS A 386 28.605 20.706 139.249 1.00 32.20 7 ATOM 1969 C LYS A 386 29.227 21.114 132.570 1.00 13.29 6 ATOM 1970 O LYS A 386 28.979 21.863 131.620 1.00 13.89 8 ATOM 1971 N LYS A 387 28.977 19.806 132.560 1.00 12.67 7 ATOM 1972 CA LYS A 387 28.362 19.128 131.418 1.00 12.88 6 ATOM 1973 CB LYS A 387 28.399 17.611 131.611 1.00 14.28 6 ATOM 1974 CG LYS A 387 29.816 17.081 131.766 1.00 13.42 6 ATOM 1975 CD LYS A 387 29.881 15.602 131.494 1.00 13.33 6 ATOM 1976 CE LYS A 387 31.227 15.024 131.884 1.00 13.20 6 ATOM 1977 NZ LYS A 387 32.390 15.534 131.080 1.00 12.97 7 ATOM 1978 C LYS A 387 26.968 19.590 131.025 1.00 12.65 6 ATOM 1979 O LYS A 387 26.661 19.694 129.833 1.00 12.93 8 ATOM 1980 N ASP A 388 26.151 19.896 132.031 1.00 12.56 7 ATOM 1981 CA ASP A 388 24.789 20.381 131.821 1.00 13.55 6 ATOM 1982 CB ASP A 388 23.944 20.110 133.079 1.00 14.06 6 ATOM 1983 CG ASP A 388 22.474 20.532 132.937 1.00 18.02 6 ATOM 1984 OD1 ASP A 388 22.077 21.141 131.919 1.00 16.44 8 ATOM 1985 OD2 ASP A 388 21.705 20.251 133.876 1.00 17.76 8 ATOM 1986 C ASP A 388 24.890 21.885 131.543 1.00 11.33 6 ATOM 1987 O ASP A 388 25.312 22.646 132.420 1.00 13.17 8 ATOM 1988 N PRO A 389 24.471 22.336 130.335 1.00 11.84 7 ATOM 1989 CD PRO A 389 23.942 21.581 129.182 1.00 11.61 6 ATOM 1990 CA PRO A 389 24.545 23.768 130.013 1.00 12.44 6 ATOM 1991 CB PRO A 389 24.076 23.826 128.557 1.00 11.08 6 ATOM 1992 CG PRO A 389 23.183 22.637 128.425 1.00 12.65 6 ATOM 1993 C PRO A 389 23.727 24.678 130.928 1.00 13.91 6 ATOM 1994 O PRO A 389 24.099 25.825 131.137 1.00 15.66 8 ATOM 1995 N LYS A 390 22.669 24.133 131.531 1.00 14.89 7 ATOM 1996 CA LYS A 390 21.822 24.900 132.447 1.00 18.49 6 ATOM 1997 CB LYS A 390 20.446 24.240 132.595 1.00 20.36 6 ATOM 1998 CG LYS A 390 19.608 24.313 131.328 1.00 24.88 6 ATOM 1999 CD LYS A 390 18.138 24.030 131.603 1.00 31.45 6 ATOM 2000 CE LYS A 390 17.287 24.269 130.357 1.00 34.46 6 ATOM 2001 NZ LYS A 390 17.324 25.694 129.893 1.00 36.88 7 ATOM 2002 C LYS A 390 22.476 25.116 133.818 1.00 18.85 6 ATOM 2003 O LYS A 390 22.147 26.072 134.523 1.00 21.71 8 ATOM 2004 N GLN A 391 23.436 24.253 134.155 1.00 18.70 7 ATOM 2005 CA GLN A 391 24.178 24.319 135.423 1.00 20.29 6 ATOM 2006 CB GLN A 391 24.394 22.908 135.994 1.00 24.00 6 ATOM 2007 CG GLN A 391 23.155 22.182 136.536 1.00 28.54 6 ATOM 2008 CD GLN A 391 23.401 20.689 136.793 1.00 31.33 6 ATOM 2009 OE1 GLN A 391 24.486 20.277 137.219 1.00 33.69 8 ATOM 2010 NE2 GLN A 391 22.391 19.870 136.510 1.00 33.04 7 ATOM 2011 C GLN A 391 25.548 24.986 135.226 1.00 18.56 6 ATOM 2012 O GLN A 391 26.238 25.306 136.202 1.00 19.95 8 ATOM 2013 N ARG A 392 25.921 25.204 133.963 1.00 16.00 7 ATOM 2014 CA ARG A 392 27.206 25.808 133.586 1.00 13.80 6 ATOM 2015 CB ARG A 392 27.457 25.592 132.084 1.00 11.11 6 ATOM 2016 CG ARG A 392 28.849 25.979 131.552 1.00 10.42 6 ATOM 2017 CD ARG A 392 29.014 25.631 130.085 1.00 9.75 6 ATOM 2018 NE ARG A 392 28.791 24.203 129.861 1.00 9.17 7 ATOM 2019 CZ ARG A 392 28.237 23.675 128.776 1.00 9.48 6 ATOM 2020 NH1 ARG A 392 27.855 24.445 127.761 1.00 10.45 7 ATOM 2021 NH2 ARG A 392 27.936 22.384 128.770 1.00 9.49 7 ATOM 2022 C ARG A 392 27.303 27.292 133.911 1.00 12.49 6 ATOM 2023 O ARG A 392 26.289 27.996 133.920 1.00 14.31 8 ATOM 2024 N LEU A 393 28.527 27.740 134.208 1.00 12.22 7 ATOM 2025 CA LEU A 393 28.818 29.144 134.488 1.00 12.00 6 ATOM 2026 CB LEU A 393 30.241 29.291 135.032 1.00 11.80 6 ATOM 2027 CG LEU A 393 30.678 30.635 135.612 1.00 14.98 6 ATOM 2028 CD1 LEU A 393 30.009 30.886 136.957 1.00 14.60 6 ATOM 2029 CD2 LEU A 393 32.181 30.638 135.762 1.00 15.42 6 ATOM 2030 C LEU A 393 28.682 29.855 133.138 1.00 12.32 6 ATOM 2031 O LEU A 393 29.406 29.548 132.185 1.00 13.80 8 ATOM 2032 N GLY A 394 27.688 30.736 133.057 1.00 13.89 7 ATOM 2033 CA GLY A 394 27.398 31.455 131.832 1.00 13.91 6 ATOM 2034 C GLY A 394 26.223 30.818 131.109 1.00 13.88 6 ATOM 2035 O GLY A 394 25.756 31.338 130.096 1.00 14.38 8 ATOM 2036 N GLY A 395 25.751 29.690 131.642 1.00 16.40 7 ATOM 2037 CA GLY A 395 24.637 28.959 131.056 1.00 16.57 6 ATOM 2038 C GLY A 395 23.267 29.427 131.505 1.00 17.44 6 ATOM 2039 O GLY A 395 22.245 28.979 130.972 1.00 18.00 8 ATOM 2040 N GLY A 396 23.255 30.316 132.497 1.00 17.83 7 ATOM 2041 CA GLY A 396 22.015 30.872 133.012 1.00 18.39 6 ATOM 2042 C GLY A 396 21.526 32.023 132.142 1.00 18.79 6 ATOM 2043 O GLY A 396 22.216 32.390 131.184 1.00 19.29 8 ATOM 2044 N PRO A 397 20.358 32.630 132.449 1.00 19.85 7 ATOM 2045 CD PRO A 397 19.396 32.200 133.483 1.00 20.34 6 ATOM 2046 CA PRO A 397 19.795 33.747 131.676 1.00 19.63 6 ATOM 2047 CB PRO A 397 18.483 34.034 132.410 1.00 19.83 6 ATOM 2048 CG PRO A 397 18.091 32.698 132.922 1.00 21.56 6 ATOM 2049 C PRO A 397 20.663 35.010 131.565 1.00 18.55 6 ATOM 2050 O PRO A 397 20.558 35.743 130.576 1.00 20.03 8 ATOM 2051 N SER A 398 21.542 35.236 132.544 1.00 17.13 7 ATOM 2052 CA SER A 398 22.404 36.421 132.529 1.00 16.53 6 ATOM 2053 CB SER A 398 22.720 36.911 133.947 1.00 18.91 6 ATOM 2054 OG SER A 398 23.578 36.030 134.640 1.00 20.93 8 ATOM 2055 C SER A 398 23.672 36.274 131.687 1.00 16.04 6 ATOM 2056 O SER A 398 24.459 37.217 131.576 1.00 15.48 8 ATOM 2057 N ASP A 399 23.863 35.078 131.118 1.00 14.87 7 ATOM 2058 CA ASP A 399 24.983 34.755 130.221 1.00 14.59 6 ATOM 2059 CB ASP A 399 24.667 35.353 128.834 1.00 14.17 6 ATOM 2060 CG ASP A 399 25.544 34.805 127.720 1.00 15.80 6 ATOM 2061 OD1 ASP A 399 25.623 33.570 127.544 1.00 16.41 8 ATOM 2062 OD2 ASP A 399 26.124 35.639 127.000 1.00 18.69 8 ATOM 2063 C ASP A 399 26.386 35.146 130.740 1.00 12.23 6 ATOM 2064 O ASP A 399 26.822 34.633 131.769 1.00 12.98 8 ATOM 2065 N ALA A 400 27.039 36.103 130.076 1.00 13.14 7 ATOM 2066 CA ALA A 400 28.384 36.561 130.436 1.00 12.17 6 ATOM 2067 CB ALA A 400 28.880 37.550 129.429 1.00 13.27 6 ATOM 2068 C ALA A 400 28.569 37.123 131.828 1.00 13.10 6 ATOM 2069 O ALA A 400 29.666 37.033 132.381 1.00 12.78 8 ATOM 2070 N LYS A 401 27.499 37.685 132.391 1.00 12.57 7 ATOM 2071 CA LYS A 401 27.531 38.265 133.736 1.00 14.04 6 ATOM 2072 CB LYS A 401 26.168 38.854 134.117 1.00 14.47 6 ATOM 2073 CG LYS A 401 26.182 39.648 135.419 1.00 17.37 6 ATOM 2074 CD LYS A 401 24.789 39.992 135.909 1.00 18.23 6 ATOM 2075 CE LYS A 401 24.858 40.652 137.276 1.00 20.09 6 ATOM 2076 NZ LYS A 401 23.517 41.067 137.773 1.00 22.39 7 ATOM 2077 C LYS A 401 27.972 37.238 134.778 1.00 13.02 6 ATOM 2078 O LYS A 401 28.780 37.560 135.643 1.00 14.28 8 ATOM 2079 N GLU A 402 27.508 35.993 134.634 1.00 13.43 7 ATOM 2080 CA GLU A 402 27.866 34.906 135.557 1.00 13.39 6 ATOM 2081 CB GLU A 402 27.106 33.619 135.221 1.00 15.35 6 ATOM 2082 CG GLU A 402 25.608 33.694 135.465 1.00 19.17 6 ATOM 2083 CD GLU A 402 24.878 32.375 135.249 1.00 22.70 6 ATOM 2084 OE1 GLU A 402 25.394 31.488 134.537 1.00 21.79 8 ATOM 2085 OE2 GLU A 402 23.768 32.224 135.800 1.00 23.82 8 ATOM 2086 C GLU A 402 29.365 34.617 135.543 1.00 12.95 6 ATOM 2087 O GLU A 402 29.967 34.405 136.596 1.00 12.71 8 ATOM 2088 N VAL A 403 29.962 34.673 134.349 1.00 11.80 7 ATOM 2089 CA VAL A 403 31.397 34.425 134.181 1.00 11.79 6 ATOM 2090 CB VAL A 403 31.780 34.132 132.697 1.00 11.12 6 ATOM 2091 CG1 VAL A 403 33.248 33.709 132.593 1.00 11.32 6 ATOM 2092 CG2 VAL A 403 30.892 33.036 132.125 1.00 9.79 6 ATOM 2093 C VAL A 403 32.194 35.616 134.701 1.00 11.20 6 ATOM 2094 O VAL A 403 33.165 35.438 135.433 1.00 11.21 8 ATOM 2095 N MET A 404 31.720 36.820 134.381 1.00 11.16 7 ATOM 2096 CA MET A 404 32.365 38.061 134.803 1.00 11.50 6 ATOM 2097 CB MET A 404 31.683 39.274 134.168 1.00 11.89 6 ATOM 2098 CG MET A 404 31.906 39.399 132.680 1.00 14.24 6 ATOM 2099 SD MET A 404 31.446 41.018 132.068 1.00 17.62 16 ATOM 2100 CE MET A 404 29.833 40.733 131.561 1.00 20.49 6 ATOM 2101 C MET A 404 32.406 38.250 136.313 1.00 12.35 6 ATOM 2102 O MET A 404 33.397 38.745 136.853 1.00 13.20 8 ATOM 2103 N GLU A 405 31.348 37.794 136.981 1.00 13.12 7 ATOM 2104 CA GLU A 405 31.226 37.916 138.428 1.00 13.47 6 ATOM 2105 CB GLU A 405 29.764 38.168 138.826 1.00 14.70 6 ATOM 2106 CG GLU A 405 29.163 39.480 138.286 1.00 20.21 6 ATOM 2107 CD GLU A 405 29.996 40.715 138.617 1.00 24.04 6 ATOM 2108 OE1 GLU A 405 30.105 41.060 139.814 1.00 27.01 8 ATOM 2109 OE2 GLU A 405 30.549 41.334 137.677 1.00 25.98 8 ATOM 2110 C GLU A 405 31.814 36.779 139.249 1.00 12.99 6 ATOM 2111 O GLU A 405 31.746 36.808 140.482 1.00 13.60 8 ATOM 2112 N HIS A 406 32.425 35.798 138.581 1.00 11.77 7 ATOM 2113 CA HIS A 406 33.043 34.669 139.284 1.00 12.70 6 ATOM 2114 CB HIS A 406 33.408 33.549 138.305 1.00 11.92 6 ATOM 2115 CG HIS A 406 33.888 32.303 138.981 1.00 12.88 6 ATOM 2116 CD2 HIS A 406 33.234 31.175 139.343 1.00 12.34 6 ATOM 2117 ND1 HIS A 406 35.182 32.160 139.434 1.00 13.21 7 ATOM 2118 CE1 HIS A 406 35.301 31.001 140.053 1.00 13.57 6 ATOM 2119 NE2 HIS A 406 34.135 30.383 140.011 1.00 11.87 7 ATOM 2120 C HIS A 406 34.291 35.162 140.032 1.00 12.02 6 ATOM 2121 O HIS A 406 35.023 36.014 139.516 1.00 12.47 8 ATOM 2122 N ARG A 407 34.521 34.620 141.235 1.00 12.75 7 ATOM 2123 CA ARG A 407 35.651 35.003 142.096 1.00 15.93 6 ATOM 2124 CB ARG A 407 35.633 34.240 143.434 1.00 18.49 6 ATOM 2125 CG ARG A 407 35.719 32.723 143.345 1.00 25.88 6 ATOM 2126 CD ARG A 407 35.841 32.085 144.723 1.00 30.52 6 ATOM 2127 NE ARG A 407 35.743 30.625 144.662 1.00 35.55 7 ATOM 2128 CZ ARG A 407 36.296 29.785 145.535 1.00 37.67 6 ATOM 2129 NH1 ARG A 407 37.007 30.240 146.562 1.00 39.58 7 ATOM 2130 NH2 ARG A 407 36.127 28.477 145.387 1.00 39.54 7 ATOM 2131 C ARG A 407 37.046 34.958 141.471 1.00 14.35 6 ATOM 2132 O ARG A 407 37.942 35.674 141.910 1.00 16.12 8 ATOM 2133 N PHE A 408 37.206 34.154 140.418 1.00 14.45 7 ATOM 2134 CA PHE A 408 38.482 34.049 139.700 1.00 13.70 6 ATOM 2135 CB PHE A 408 38.410 32.940 138.633 1.00 12.40 6 ATOM 2136 CG PHE A 408 39.674 32.783 137.816 1.00 12.58 6 ATOM 2137 CD1 PHE A 408 40.783 32.096 138.336 1.00 14.90 6 ATOM 2138 CD2 PHE A 408 39.761 33.335 136.526 1.00 13.08 6 ATOM 2139 CE1 PHE A 408 41.979 31.951 137.580 1.00 14.82 6 ATOM 2140 CE2 PHE A 408 40.941 33.203 135.757 1.00 13.94 6 ATOM 2141 CZ PHE A 408 42.057 32.508 136.285 1.00 12.78 6 ATOM 2142 C PHE A 408 38.809 35.395 139.042 1.00 13.42 6 ATOM 2143 O PHE A 408 39.977 35.760 138.923 1.00 13.39 8 ATOM 2144 N PHE A 409 37.762 36.113 138.634 1.00 13.10 7 ATOM 2145 CA PHE A 409 37.901 37.407 137.976 1.00 13.41 6 ATOM 2146 CB PHE A 409 36.951 37.481 136.768 1.00 13.84 6 ATOM 2147 CG PHE A 409 37.344 36.594 135.611 1.00 12.15 6 ATOM 2148 CD1 PHE A 409 36.496 35.552 135.198 1.00 12.18 6 ATOM 2149 CD2 PHE A 409 38.542 36.815 134.906 1.00 11.87 6 ATOM 2150 CE1 PHE A 409 36.831 34.728 134.086 1.00 11.64 6 ATOM 2151 CE2 PHE A 409 38.899 36.001 133.786 1.00 12.09 6 ATOM 2152 CZ PHE A 409 38.040 34.956 133.378 1.00 10.57 6 ATOM 2153 C PHE A 409 37.667 38.618 138.895 1.00 14.52 6 ATOM 2154 O PHE A 409 37.428 39.722 138.408 1.00 14.19 8 ATOM 2155 N LEU A 410 37.787 38.421 140.211 1.00 15.05 7 ATOM 2156 CA LEU A 410 37.579 39.490 141.208 1.00 18.50 6 ATOM 2157 CB LEU A 410 37.760 38.929 142.628 1.00 21.40 6 ATOM 2158 CG LEU A 410 37.296 39.735 143.852 1.00 25.18 6 ATOM 2159 CD1 LEU A 410 35.773 39.743 143.935 1.00 26.48 6 ATOM 2160 CD2 LEU A 410 37.886 39.125 145.115 1.00 27.65 6 ATOM 2161 C LEU A 410 38.478 40.726 141.017 1.00 18.38 6 ATOM 2162 O LEU A 410 38.024 41.863 141.193 1.00 19.40 8 ATOM 2163 N SER A 411 39.715 40.491 140.578 1.00 17.42 7 ATOM 2164 CA SER A 411 40.704 41.551 140.352 1.00 18.35 6 ATOM 2165 CB SER A 411 42.117 40.956 140.400 1.00 19.31 6 ATOM 2166 OG SER A 411 42.334 40.058 139.322 1.00 20.74 8 ATOM 2167 C SER A 411 40.518 42.312 139.034 1.00 17.94 6 ATOM 2168 O SER A 411 41.209 43.303 138.778 1.00 20.07 8 ATOM 2169 N ILE A 412 39.584 41.840 138.210 1.00 17.11 7 ATOM 2170 CA ILE A 412 39.315 42.434 136.905 1.00 16.59 6 ATOM 2171 CB ILE A 412 38.934 41.321 135.853 1.00 16.81 6 ATOM 2172 CG2 ILE A 412 38.582 41.918 134.495 1.00 16.59 6 ATOM 2173 CG1 ILE A 412 40.065 40.287 135.703 1.00 17.73 6 ATOM 2174 CD1 ILE A 412 41.389 40.816 135.130 1.00 18.96 6 ATOM 2175 C ILE A 412 38.253 43.540 136.897 1.00 15.40 6 ATOM 2176 O ILE A 412 37.149 43.375 137.422 1.00 15.80 8 ATOM 2177 N ASN A 413 38.629 44.671 136.304 1.00 15.27 7 ATOM 2178 CA ASN A 413 37.739 45.815 136.108 1.00 15.14 6 ATOM 2179 CB ASN A 413 38.491 47.136 136.351 1.00 17.12 6 ATOM 2180 CG ASN A 413 37.636 48.377 136.074 1.00 19.49 6 ATOM 2181 OD1 ASN A 413 37.030 48.513 135.010 1.00 18.40 8 ATOM 2182 ND2 ASN A 413 37.625 49.306 137.019 1.00 21.92 7 ATOM 2183 C ASN A 413 37.390 45.631 134.626 1.00 13.67 6 ATOM 2184 O ASN A 413 38.255 45.778 133.757 1.00 14.06 8 ATOM 2185 N TRP A 414 36.130 45.295 134.358 1.00 13.63 7 ATOM 2186 CA TRP A 414 35.648 45.028 133.002 1.00 12.97 6 ATOM 2187 CB TRP A 414 34.303 44.298 133.051 1.00 12.80 6 ATOM 2188 CG TRP A 414 34.460 42.951 133.696 1.00 13.87 6 ATOM 2189 CD2 TRP A 414 35.000 41.772 133.088 1.00 12.09 6 ATOM 2190 CE2 TRP A 414 35.138 40.797 134.115 1.00 11.46 6 ATOM 2191 CE3 TRP A 414 35.393 41.441 131.774 1.00 11.83 6 ATOM 2192 CD1 TRP A 414 34.272 42.644 135.021 1.00 13.16 6 ATOM 2193 NE1 TRP A 414 34.685 41.359 135.279 1.00 11.96 7 ATOM 2194 CZ2 TRP A 414 35.660 39.508 133.869 1.00 11.91 6 ATOM 2195 CZ3 TRP A 414 35.911 40.159 131.527 1.00 11.71 6 ATOM 2196 CH2 TRP A 414 36.039 39.207 132.579 1.00 10.39 6 ATOM 2197 C TRP A 414 35.656 46.159 131.989 1.00 14.70 6 ATOM 2198 O TRP A 414 35.728 45.908 130.779 1.00 13.36 8 ATOM 2199 N GLN A 415 35.625 47.398 132.478 1.00 15.55 7 ATOM 2200 CA GLN A 415 35.690 48.554 131.594 1.00 17.40 6 ATOM 2201 CB GLN A 415 35.081 49.802 132.244 1.00 19.34 6 ATOM 2202 CG GLN A 415 33.548 49.789 132.319 1.00 23.34 6 ATOM 2203 CD GLN A 415 32.847 49.801 130.951 1.00 27.24 6 ATOM 2204 OE1 GLN A 415 33.367 50.334 129.965 1.00 28.76 8 ATOM 2205 NE2 GLN A 415 31.651 49.219 130.900 1.00 27.62 7 ATOM 2206 C GLN A 415 37.137 48.793 131.172 1.00 17.70 6 ATOM 2207 O GLN A 415 37.388 49.190 130.036 1.00 19.63 8 ATOM 2208 N ASP A 416 38.079 48.458 132.060 1.00 16.94 7 ATOM 2209 CA ASP A 416 39.518 48.584 131.788 1.00 16.83 6 ATOM 2210 CB ASP A 416 40.350 48.351 133.054 1.00 18.62 6 ATOM 2211 CG ASP A 416 40.379 49.555 133.987 1.00 19.84 6 ATOM 2212 OD1 ASP A 416 39.757 50.595 133.683 1.00 21.92 8 ATOM 2213 OD2 ASP A 416 41.029 49.445 135.046 1.00 21.80 8 ATOM 2214 C ASP A 416 39.944 47.563 130.733 1.00 17.25 6 ATOM 2215 O ASP A 416 40.854 47.820 129.944 1.00 18.22 8 ATOM 2216 N VAL A 417 39.263 46.413 130.728 1.00 17.39 7 ATOM 2217 CA VAL A 417 39.530 45.331 129.772 1.00 16.75 6 ATOM 2218 CB VAL A 417 38.769 44.023 130.160 1.00 17.26 6 ATOM 2219 CG1 VAL A 417 38.917 42.936 129.088 1.00 16.25 6 ATOM 2220 CG2 VAL A 417 39.317 43.492 131.448 1.00 16.17 6 ATOM 2221 C VAL A 417 39.172 45.770 128.353 1.00 17.99 6 ATOM 2222 O VAL A 417 40.056 45.833 127.503 1.00 18.75 8 ATOM 2223 N VAL A 418 37.909 46.159 128.139 1.00 18.28 7 ATOM 2224 CA VAL A 418 37.418 46.587 126.822 1.00 19.90 6 ATOM 2225 CB VAL A 418 35.842 46.662 126.788 1.00 19.64 6 ATOM 2226 CG1 VAL A 418 35.305 47.835 127.604 1.00 19.84 6 ATOM 2227 CG2 VAL A 418 35.321 46.704 125.352 1.00 20.16 6 ATOM 2228 C VAL A 418 38.078 47.871 126.291 1.00 19.90 6 ATOM 2229 O VAL A 418 38.198 48.055 125.081 1.00 21.00 8 ATOM 2230 N GLN A 419 38.553 48.719 127.202 1.00 20.33 7 ATOM 2231 CA GLN A 419 39.213 49.967 126.817 1.00 21.79 6 ATOM 2232 CB GLN A 419 38.866 51.088 127.808 1.00 23.08 6 ATOM 2233 CG GLN A 419 37.417 51.577 127.693 1.00 24.81 6 ATOM 2234 CD GLN A 419 37.024 52.558 128.787 1.00 27.75 6 ATOM 2235 OE1 GLN A 419 36.120 52.290 129.581 1.00 29.19 8 ATOM 2236 NE2 GLN A 419 37.690 53.706 128.822 1.00 29.16 7 ATOM 2237 C GLN A 419 40.729 49.824 126.641 1.00 22.34 6 ATOM 2238 O GLN A 419 41.423 50.816 126.399 1.00 22.02 8 ATOM 2239 N LYS A 420 41.220 48.578 126.720 1.00 22.05 7 ATOM 2240 CA LYS A 420 42.645 48.215 126.567 1.00 22.92 6 ATOM 2241 CB LYS A 420 43.116 48.414 125.112 1.00 25.23 6 ATOM 2242 CG LYS A 420 42.651 47.388 124.095 1.00 29.12 6 ATOM 2243 CD LYS A 420 43.203 47.780 122.733 1.00 32.19 6 ATOM 2244 CE LYS A 420 43.098 46.673 121.711 1.00 36.00 6 ATOM 2245 NZ LYS A 420 43.592 47.147 120.385 1.00 38.11 7 ATOM 2246 C LYS A 420 43.611 48.936 127.525 1.00 23.62 6 ATOM 2247 O LYS A 420 44.762 49.213 127.166 1.00 22.55 8 ATOM 2248 N LYS A 421 43.145 49.212 128.744 1.00 22.95 7 ATOM 2249 CA LYS A 421 43.943 49.916 129.753 1.00 23.80 6 ATOM 2250 CB LYS A 421 43.036 50.605 130.776 1.00 24.28 6 ATOM 2251 CG LYS A 421 42.209 51.749 130.217 1.00 25.04 6 ATOM 2252 CD LYS A 421 41.417 52.430 131.318 1.00 26.69 6 ATOM 2253 CE LYS A 421 40.519 53.508 130.754 1.00 28.22 6 ATOM 2254 NZ LYS A 421 39.720 54.179 131.815 1.00 30.83 7 ATOM 2255 C LYS A 421 44.967 49.060 130.489 1.00 24.93 6 ATOM 2256 O LYS A 421 45.931 49.589 131.048 1.00 26.67 8 ATOM 2257 N LEU A 422 44.764 47.743 130.474 1.00 25.51 7 ATOM 2258 CA LEU A 422 45.664 46.813 131.152 1.00 25.66 6 ATOM 2259 CB LEU A 422 44.901 45.556 131.585 1.00 27.00 6 ATOM 2260 CG LEU A 422 43.710 45.738 132.539 1.00 27.92 6 ATOM 2261 CD1 LEU A 422 42.975 44.421 132.699 1.00 28.25 6 ATOM 2262 CD2 LEU A 422 44.166 46.266 133.900 1.00 29.05 6 ATOM 2263 C LEU A 422 46.899 46.445 130.329 1.00 25.15 6 ATOM 2264 O LEU A 422 46.830 46.339 129.099 1.00 26.00 8 ATOM 2265 N LEU A 423 48.023 46.286 131.028 1.00 24.13 7 ATOM 2266 CA LEU A 423 49.319 45.941 130.434 1.00 22.43 6 ATOM 2267 CB LEU A 423 50.458 46.327 131.399 1.00 24.35 6 ATOM 2268 CG LEU A 423 51.937 46.016 131.090 1.00 26.02 6 ATOM 2269 CD1 LEU A 423 52.460 46.882 129.956 1.00 27.11 6 ATOM 2270 CD2 LEU A 423 52.782 46.231 132.336 1.00 28.32 6 ATOM 2271 C LEU A 423 49.414 44.448 130.085 1.00 20.23 6 ATOM 2272 O LEU A 423 49.274 43.595 130.972 1.00 18.57 8 ATOM 2273 N PRO A 424 49.653 44.114 128.792 1.00 18.68 7 ATOM 2274 CD PRO A 424 49.663 45.008 127.616 1.00 17.86 6 ATOM 2275 CA PRO A 424 49.770 42.714 128.355 1.00 16.97 6 ATOM 2276 CB PRO A 424 49.949 42.844 126.840 1.00 16.81 6 ATOM 2277 CG PRO A 424 49.191 44.092 126.521 1.00 18.42 6 ATOM 2278 C PRO A 424 50.962 42.001 129.009 1.00 17.48 6 ATOM 2279 O PRO A 424 52.030 42.594 129.155 1.00 17.80 8 ATOM 2280 N PRO A 425 50.776 40.739 129.460 1.00 16.81 7 ATOM 2281 CD PRO A 425 49.510 39.988 129.491 1.00 17.80 6 ATOM 2282 CA PRO A 425 51.835 39.955 130.104 1.00 16.74 6 ATOM 2283 CB PRO A 425 51.068 38.759 130.668 1.00 17.34 6 ATOM 2284 CG PRO A 425 49.960 38.578 129.691 1.00 16.88 6 ATOM 2285 C PRO A 425 52.950 39.524 129.154 1.00 16.72 6 ATOM 2286 O PRO A 425 53.997 39.042 129.587 1.00 18.53 8 ATOM 2287 N PHE A 426 52.705 39.720 127.860 1.00 16.03 7 ATOM 2288 CA PHE A 426 53.647 39.380 126.807 1.00 16.86 6 ATOM 2289 CB PHE A 426 53.472 37.900 126.391 1.00 18.58 6 ATOM 2290 CG PHE A 426 54.368 37.463 125.252 1.00 21.11 6 ATOM 2291 CD1 PHE A 426 55.749 37.280 125.456 1.00 23.40 6 ATOM 2292 CD2 PHE A 426 53.836 37.264 123.962 1.00 22.08 6 ATOM 2293 CE1 PHE A 426 56.604 36.905 124.385 1.00 24.63 6 ATOM 2294 CE2 PHE A 426 54.674 36.893 122.881 1.00 23.50 6 ATOM 2295 CZ PHE A 426 56.063 36.713 123.092 1.00 23.30 6 ATOM 2296 C PHE A 426 53.400 40.287 125.608 1.00 18.12 6 ATOM 2297 O PHE A 426 52.266 40.416 125.139 1.00 17.87 8 ATOM 2298 N LYS A 427 54.468 40.914 125.124 1.00 17.18 7 ATOM 2299 CA LYS A 427 54.377 41.749 123.941 1.00 18.16 6 ATOM 2300 CB LYS A 427 54.895 43.179 124.178 1.00 21.73 6 ATOM 2301 CG LYS A 427 54.647 44.095 122.962 1.00 23.52 6 ATOM 2302 CD LYS A 427 55.229 45.485 123.092 1.00 27.95 6 ATOM 2303 CE LYS A 427 55.030 46.241 121.784 1.00 28.82 6 ATOM 2304 NZ LYS A 427 55.462 47.660 121.853 1.00 29.78 7 ATOM 2305 C LYS A 427 55.215 41.054 122.869 1.00 17.62 6 ATOM 2306 O LYS A 427 56.379 40.711 123.115 1.00 16.79 8 ATOM 2307 N PRO A 428 54.607 40.752 121.698 1.00 17.15 7 ATOM 2308 CD PRO A 428 53.163 40.831 121.405 1.00 17.03 6 ATOM 2309 CA PRO A 428 55.299 40.097 120.586 1.00 17.28 6 ATOM 2310 CB PRO A 428 54.235 40.093 119.499 1.00 17.51 6 ATOM 2311 CG PRO A 428 53.008 39.854 120.282 1.00 17.41 6 ATOM 2312 C PRO A 428 56.537 40.882 120.157 1.00 17.75 6 ATOM 2313 O PRO A 428 56.467 42.095 119.946 1.00 18.21 8 ATOM 2314 N GLN A 429 57.671 40.188 120.099 1.00 18.76 7 ATOM 2315 CA GLN A 429 58.946 40.801 119.738 1.00 21.29 6 ATOM 2316 CB GLN A 429 60.090 40.138 120.527 1.00 22.56 6 ATOM 2317 CG GLN A 429 59.980 40.269 122.050 1.00 25.44 6 ATOM 2318 CD GLN A 429 60.068 41.708 122.539 1.00 27.92 6 ATOM 2319 OE1 GLN A 429 61.147 42.301 122.574 1.00 30.19 8 ATOM 2320 NE2 GLN A 429 58.930 42.270 122.933 1.00 28.12 7 ATOM 2321 C GLN A 429 59.247 40.828 118.238 1.00 22.96 6 ATOM 2322 O GLN A 429 60.343 40.468 117.800 1.00 23.75 8 ATOM 2323 N VAL A 430 58.271 41.295 117.460 1.00 23.88 7 ATOM 2324 CA VAL A 430 58.410 41.406 116.008 1.00 26.08 6 ATOM 2325 CB VAL A 430 57.025 41.379 115.275 1.00 26.03 6 ATOM 2326 CG1 VAL A 430 56.450 39.969 115.311 1.00 25.78 6 ATOM 2327 CG2 VAL A 430 56.031 42.359 115.908 1.00 26.26 6 ATOM 2328 C VAL A 430 59.212 42.659 115.643 1.00 27.98 6 ATOM 2329 O VAL A 430 58.989 43.733 116.211 1.00 28.95 8 ATOM 2330 N THR A 431 60.181 42.489 114.744 1.00 29.32 7 ATOM 2331 CA THR A 431 61.063 43.575 114.302 1.00 31.97 6 ATOM 2332 CB THR A 431 62.501 43.061 114.059 1.00 32.02 6 ATOM 2333 OG1 THR A 431 62.469 41.929 113.181 1.00 32.45 8 ATOM 2334 CG2 THR A 431 63.161 42.668 115.380 1.00 32.42 6 ATOM 2335 C THR A 431 60.571 44.322 113.060 1.00 33.55 6 ATOM 2336 O THR A 431 61.073 45.403 112.734 1.00 34.02 8 ATOM 2337 N SER A 432 59.604 43.719 112.371 1.00 34.53 7 ATOM 2338 CA SER A 432 58.995 44.280 111.165 1.00 35.56 6 ATOM 2339 CB SER A 432 59.825 43.930 109.919 1.00 35.93 6 ATOM 2340 OG SER A 432 59.979 42.529 109.764 1.00 36.58 8 ATOM 2341 C SER A 432 57.582 43.720 111.032 1.00 35.97 6 ATOM 2342 O SER A 432 57.202 42.800 111.762 1.00 36.11 8 ATOM 2343 N GLU A 433 56.814 44.269 110.092 1.00 36.18 7 ATOM 2344 CA GLU A 433 55.441 43.824 109.848 1.00 36.13 6 ATOM 2345 CB GLU A 433 54.633 44.944 109.186 1.00 39.01 6 ATOM 2346 CG GLU A 433 54.144 46.052 110.124 1.00 42.48 6 ATOM 2347 CD GLU A 433 52.986 45.619 111.020 1.00 45.05 6 ATOM 2348 OE1 GLU A 433 51.966 45.120 110.494 1.00 45.27 8 ATOM 2349 OE2 GLU A 433 53.096 45.786 112.254 1.00 47.56 8 ATOM 2350 C GLU A 433 55.379 42.544 109.007 1.00 34.71 6 ATOM 2351 O GLU A 433 54.308 41.961 108.828 1.00 36.08 8 ATOM 2352 N VAL A 434 56.544 42.104 108.530 1.00 32.15 7 ATOM 2353 CA VAL A 434 56.680 40.897 107.719 1.00 29.73 6 ATOM 2354 CB VAL A 434 57.485 41.211 106.397 1.00 30.54 6 ATOM 2355 CG1 VAL A 434 58.984 41.409 106.670 1.00 29.95 6 ATOM 2356 CG2 VAL A 434 57.234 40.155 105.334 1.00 31.86 6 ATOM 2357 C VAL A 434 57.307 39.751 108.547 1.00 28.24 6 ATOM 2358 O VAL A 434 57.457 38.627 108.067 1.00 28.54 8 ATOM 2359 N ASP A 435 57.640 40.052 109.805 1.00 26.14 7 ATOM 2360 CA ASP A 435 58.244 39.093 110.738 1.00 23.40 6 ATOM 2361 CB ASP A 435 58.846 39.864 111.928 1.00 22.35 6 ATOM 2362 CG ASP A 435 59.679 38.990 112.870 1.00 22.38 6 ATOM 2363 OD1 ASP A 435 59.610 37.744 112.813 1.00 20.66 8 ATOM 2364 OD2 ASP A 435 60.407 39.577 113.696 1.00 23.00 8 ATOM 2365 C ASP A 435 57.176 38.088 111.205 1.00 21.89 6 ATOM 2366 O ASP A 435 56.246 38.446 111.931 1.00 22.64 8 ATOM 2367 N THR A 436 57.334 36.834 110.777 1.00 19.33 7 ATOM 2368 CA THR A 436 56.393 35.760 111.114 1.00 17.47 6 ATOM 2369 CB THR A 436 55.869 35.056 109.832 1.00 17.56 6 ATOM 2370 OG1 THR A 436 56.974 34.595 109.044 1.00 19.37 8 ATOM 2371 CG2 THR A 436 55.015 35.996 109.005 1.00 18.19 6 ATOM 2372 C THR A 436 56.956 34.709 112.083 1.00 15.69 6 ATOM 2373 O THR A 436 56.560 33.537 112.038 1.00 14.91 8 ATOM 2374 N ARG A 437 57.810 35.150 113.010 1.00 15.42 7 ATOM 2375 CA ARG A 437 58.444 34.264 113.998 1.00 14.40 6 ATOM 2376 CB ARG A 437 59.493 35.028 114.821 1.00 14.85 6 ATOM 2377 CG ARG A 437 58.920 36.112 115.723 1.00 16.75 6 ATOM 2378 CD ARG A 437 59.975 36.735 116.598 1.00 17.36 6 ATOM 2379 NE ARG A 437 60.808 37.670 115.854 1.00 17.47 7 ATOM 2380 CZ ARG A 437 62.004 38.091 116.252 1.00 16.94 6 ATOM 2381 NH1 ARG A 437 62.527 37.656 117.391 1.00 16.57 7 ATOM 2382 NH2 ARG A 437 62.655 38.986 115.526 1.00 20.39 7 ATOM 2383 C ARG A 437 57.467 33.557 114.951 1.00 13.96 6 ATOM 2384 O ARG A 437 57.835 32.585 115.613 1.00 15.31 8 ATOM 2385 N TYR A 438 56.236 34.062 115.017 1.00 14.57 7 ATOM 2386 CA TYR A 438 55.222 33.483 115.894 1.00 13.55 6 ATOM 2387 CB TYR A 438 54.527 34.570 116.710 1.00 13.94 6 ATOM 2388 CG TYR A 438 55.464 35.303 117.641 1.00 12.64 6 ATOM 2389 CD1 TYR A 438 55.630 36.692 117.537 1.00 13.96 6 ATOM 2390 CE1 TYR A 438 56.528 37.382 118.381 1.00 14.91 6 ATOM 2391 CD2 TYR A 438 56.215 34.608 118.617 1.00 14.88 6 ATOM 2392 CE2 TYR A 438 57.114 35.291 119.476 1.00 14.08 6 ATOM 2393 CZ TYR A 438 57.260 36.676 119.348 1.00 14.78 6 ATOM 2394 OH TYR A 438 58.107 37.359 120.187 1.00 15.81 8 ATOM 2395 C TYR A 438 54.225 32.572 115.196 1.00 14.68 6 ATOM 2396 O TYR A 438 53.168 32.235 115.740 1.00 12.73 8 ATOM 2397 N PHE A 439 54.580 32.189 113.973 1.00 14.15 7 ATOM 2398 CA PHE A 439 53.787 31.275 113.163 1.00 15.36 6 ATOM 2399 CB PHE A 439 53.349 31.944 111.857 1.00 13.44 6 ATOM 2400 CG PHE A 439 52.313 33.011 112.048 1.00 14.94 6 ATOM 2401 CD1 PHE A 439 52.695 34.342 112.321 1.00 14.25 6 ATOM 2402 CD2 PHE A 439 50.944 32.690 111.983 1.00 13.54 6 ATOM 2403 CE1 PHE A 439 51.722 35.352 112.531 1.00 14.39 6 ATOM 2404 CE2 PHE A 439 49.951 33.685 112.189 1.00 13.82 6 ATOM 2405 CZ PHE A 439 50.343 35.022 112.465 1.00 14.08 6 ATOM 2406 C PHE A 439 54.671 30.070 112.902 1.00 15.29 6 ATOM 2407 O PHE A 439 55.891 30.210 112.775 1.00 16.46 8 ATOM 2408 N ASP A 440 54.064 28.883 112.886 1.00 17.46 7 ATOM 2409 CA ASP A 440 54.794 27.630 112.672 1.00 19.37 6 ATOM 2410 CB ASP A 440 53.867 26.425 112.856 1.00 20.52 6 ATOM 2411 CG ASP A 440 53.386 26.274 114.283 1.00 25.24 6 ATOM 2412 OD1 ASP A 440 52.170 26.432 114.516 1.00 27.53 8 ATOM 2413 OD2 ASP A 440 54.224 26.011 115.174 1.00 26.15 8 ATOM 2414 C ASP A 440 55.493 27.539 111.323 1.00 20.61 6 ATOM 2415 O ASP A 440 54.945 27.961 110.299 1.00 19.75 8 ATOM 2416 N ASP A 441 56.710 26.989 111.350 1.00 22.10 7 ATOM 2417 CA ASP A 441 57.548 26.804 110.160 1.00 24.42 6 ATOM 2418 CB ASP A 441 58.935 26.272 110.551 1.00 27.70 6 ATOM 2419 CG ASP A 441 59.777 27.300 111.297 1.00 31.13 6 ATOM 2420 OD1 ASP A 441 59.750 28.496 110.925 1.00 33.15 8 ATOM 2421 OD2 ASP A 441 60.479 26.907 112.257 1.00 34.67 8 ATOM 2422 C ASP A 441 56.910 25.886 109.117 1.00 23.54 6 ATOM 2423 O ASP A 441 57.206 25.999 107.931 1.00 23.53 8 ATOM 2424 N GLU A 442 55.981 25.038 109.570 1.00 22.83 7 ATOM 2425 CA GLU A 442 55.240 24.098 108.721 1.00 24.27 6 ATOM 2426 CB GLU A 442 54.275 23.260 109.583 1.00 26.34 6 ATOM 2427 CG GLU A 442 53.650 22.040 108.877 1.00 32.64 6 ATOM 2428 CD GLU A 442 52.460 21.427 109.624 1.00 35.15 6 ATOM 2429 OE1 GLU A 442 52.362 21.565 110.866 1.00 36.85 8 ATOM 2430 OE2 GLU A 442 51.616 20.786 108.959 1.00 37.07 8 ATOM 2431 C GLU A 442 54.443 24.870 107.659 1.00 23.04 6 ATOM 2432 O GLU A 442 54.279 24.402 106.533 1.00 23.83 8 ATOM 2433 N PHE A 443 54.010 26.078 108.024 1.00 22.04 7 ATOM 2434 CA PHE A 443 53.231 26.940 107.140 1.00 20.72 6 ATOM 2435 CB PHE A 443 52.068 27.577 107.913 1.00 20.35 6 ATOM 2436 CG PHE A 443 51.198 26.573 108.616 1.00 20.33 6 ATOM 2437 CD1 PHE A 443 51.176 26.511 110.021 1.00 21.78 6 ATOM 2438 CD2 PHE A 443 50.455 25.630 107.877 1.00 21.44 6 ATOM 2439 CE1 PHE A 443 50.431 25.512 110.693 1.00 21.60 6 ATOM 2440 CE2 PHE A 443 49.703 24.623 108.525 1.00 21.37 6 ATOM 2441 CZ PHE A 443 49.691 24.560 109.935 1.00 20.86 6 ATOM 2442 C PHE A 443 54.033 28.017 106.412 1.00 20.98 6 ATOM 2443 O PHE A 443 53.922 28.139 105.193 1.00 21.49 8 ATOM 2444 N THR A 444 54.874 28.748 107.147 1.00 21.52 7 ATOM 2445 CA THR A 444 55.676 29.844 106.583 1.00 22.58 6 ATOM 2446 CB THR A 444 56.322 30.718 107.683 1.00 22.02 6 ATOM 2447 OG1 THR A 444 57.239 29.934 108.456 1.00 21.75 8 ATOM 2448 CG2 THR A 444 55.254 31.305 108.595 1.00 21.35 6 ATOM 2449 C THR A 444 56.749 29.473 105.560 1.00 24.72 6 ATOM 2450 O THR A 444 57.153 30.319 104.757 1.00 25.44 8 ATOM 2451 N ALA A 445 57.190 28.216 105.590 1.00 27.35 7 ATOM 2452 CA ALA A 445 58.215 27.718 104.669 1.00 29.67 6 ATOM 2453 CB ALA A 445 59.021 26.608 105.329 1.00 29.94 6 ATOM 2454 C ALA A 445 57.639 27.235 103.335 1.00 31.56 6 ATOM 2455 O ALA A 445 58.386 27.037 102.373 1.00 31.66 8 ATOM 2456 N GLN A 446 56.314 27.071 103.283 1.00 33.18 7 ATOM 2457 CA GLN A 446 55.610 26.613 102.081 1.00 34.77 6 ATOM 2458 CB GLN A 446 54.187 26.159 102.421 1.00 34.24 6 ATOM 2459 CG GLN A 446 54.093 24.839 103.169 1.00 34.08 6 ATOM 2460 CD GLN A 446 52.656 24.415 103.435 1.00 33.29 6 ATOM 2461 OE1 GLN A 446 52.269 24.175 104.578 1.00 33.90 8 ATOM 2462 NE2 GLN A 446 51.857 24.326 102.377 1.00 33.08 7 ATOM 2463 C GLN A 446 55.545 27.674 100.988 1.00 37.22 6 ATOM 2464 O GLN A 446 55.373 28.863 101.270 1.00 36.65 8 ATOM 2465 N SER A 447 55.689 27.224 99.742 1.00 39.80 7 ATOM 2466 CA SER A 447 55.650 28.101 98.575 1.00 43.00 6 ATOM 2467 CB SER A 447 56.457 27.493 97.420 1.00 43.75 6 ATOM 2468 OG SER A 447 56.001 26.188 97.094 1.00 45.50 8 ATOM 2469 C SER A 447 54.216 28.374 98.131 1.00 44.41 6 ATOM 2470 O SER A 447 53.360 27.483 98.179 1.00 45.14 8 ATOM 2471 N ILE A 448 53.959 29.624 97.752 1.00 46.01 7 ATOM 2472 CA ILE A 448 52.643 30.060 97.285 1.00 47.46 6 ATOM 2473 CB ILE A 448 52.031 31.175 98.201 1.00 47.29 6 ATOM 2474 CG2 ILE A 448 51.337 30.536 99.406 1.00 48.10 6 ATOM 2475 CG1 ILE A 448 53.105 32.181 98.648 1.00 47.36 6 ATOM 2476 CD1 ILE A 448 52.556 33.471 99.191 1.00 46.46 6 ATOM 2477 C ILE A 448 52.696 30.500 95.814 1.00 48.18 6 ATOM 2478 O ILE A 448 53.031 31.648 95.496 1.00 48.99 8 ATOM 2479 N ALA A 449 52.404 29.552 94.924 1.00 48.93 7 ATOM 2480 CA ALA A 449 52.415 29.790 93.480 1.00 49.14 6 ATOM 2481 CB ALA A 449 52.965 28.568 92.752 1.00 49.68 6 ATOM 2482 C ALA A 449 51.033 30.154 92.940 1.00 49.19 6 ATOM 2483 O ALA A 449 50.026 29.563 93.328 1.00 49.36 8 ATOM 2484 N ALA A 467 26.085 37.489 90.928 1.00 56.86 7 ATOM 2485 CA ALA A 467 26.405 36.169 91.459 1.00 56.70 6 ATOM 2486 CB ALA A 467 27.546 36.271 92.469 1.00 56.87 6 ATOM 2487 C ALA A 467 25.183 35.509 92.099 1.00 56.46 6 ATOM 2488 O ALA A 467 24.986 34.297 91.953 1.00 56.38 8 ATOM 2489 N ALA A 468 24.387 36.318 92.812 1.00 56.14 7 ATOM 2490 CA ALA A 468 23.151 35.924 93.521 1.00 55.79 6 ATOM 2491 CB ALA A 468 22.094 35.367 92.542 1.00 55.99 6 ATOM 2492 C ALA A 468 23.314 34.988 94.725 1.00 55.45 6 ATOM 2493 O ALA A 468 22.611 35.133 95.732 1.00 55.63 8 ATOM 2494 N MET A 469 24.245 34.042 94.611 1.00 54.52 7 ATOM 2495 CA MET A 469 24.543 33.059 95.652 1.00 54.01 6 ATOM 2496 CB MET A 469 25.212 31.837 95.002 1.00 54.95 6 ATOM 2497 CG MET A 469 25.428 30.627 95.906 1.00 56.40 6 ATOM 2498 SD MET A 469 25.584 29.048 95.022 1.00 58.48 16 ATOM 2499 CE MET A 469 26.801 29.442 93.747 1.00 58.56 6 ATOM 2500 C MET A 469 25.429 33.677 96.746 1.00 53.03 6 ATOM 2501 O MET A 469 25.208 33.444 97.939 1.00 53.08 8 ATOM 2502 N PHE A 470 26.408 34.478 96.321 1.00 51.14 7 ATOM 2503 CA PHE A 470 27.333 35.167 97.226 1.00 49.71 6 ATOM 2504 CB PHE A 470 28.794 34.839 96.859 1.00 48.67 6 ATOM 2505 CG PHE A 470 29.145 33.374 96.948 1.00 47.86 6 ATOM 2506 CD1 PHE A 470 29.304 32.745 98.199 1.00 47.32 6 ATOM 2507 CD2 PHE A 470 29.334 32.616 95.775 1.00 47.25 6 ATOM 2508 CE1 PHE A 470 29.650 31.366 98.288 1.00 46.97 6 ATOM 2509 CE2 PHE A 470 29.680 31.236 95.840 1.00 46.76 6 ATOM 2510 CZ PHE A 470 29.838 30.610 97.102 1.00 46.81 6 ATOM 2511 C PHE A 470 27.077 36.681 97.125 1.00 49.28 6 ATOM 2512 O PHE A 470 28.002 37.478 96.928 1.00 49.59 8 ATOM 2513 N ALA A 471 25.805 37.060 97.271 1.00 48.79 7 ATOM 2514 CA ALA A 471 25.357 38.455 97.187 1.00 48.14 6 ATOM 2515 CB ALA A 471 23.856 38.504 96.915 1.00 48.35 6 ATOM 2516 C ALA A 471 25.698 39.318 98.403 1.00 47.44 6 ATOM 2517 O ALA A 471 26.031 40.498 98.258 1.00 47.41 8 ATOM 2518 N ASP A 472 25.625 38.719 99.591 1.00 46.10 7 ATOM 2519 CA ASP A 472 25.912 39.418 100.846 1.00 45.08 6 ATOM 2520 CB ASP A 472 24.947 38.924 101.938 1.00 47.05 6 ATOM 2521 CG ASP A 472 24.541 40.021 102.913 1.00 49.57 6 ATOM 2522 OD1 ASP A 472 25.422 40.578 103.606 1.00 51.07 8 ATOM 2523 OD2 ASP A 472 23.331 40.319 102.992 1.00 51.55 8 ATOM 2524 C ASP A 472 27.376 39.233 101.287 1.00 42.55 6 ATOM 2525 O ASP A 472 27.714 39.448 102.456 1.00 42.36 8 ATOM 2526 N PHE A 473 28.242 38.880 100.335 1.00 39.70 7 ATOM 2527 CA PHE A 473 29.662 38.651 100.612 1.00 36.81 6 ATOM 2528 CB PHE A 473 30.232 37.578 99.662 1.00 35.11 6 ATOM 2529 CG PHE A 473 31.549 36.995 100.115 1.00 32.53 6 ATOM 2530 CD1 PHE A 473 31.574 35.931 101.035 1.00 32.46 6 ATOM 2531 CD2 PHE A 473 32.775 37.545 99.674 1.00 31.94 6 ATOM 2532 CE1 PHE A 473 32.801 35.422 101.522 1.00 30.28 6 ATOM 2533 CE2 PHE A 473 34.014 37.050 100.152 1.00 31.33 6 ATOM 2534 CZ PHE A 473 34.026 35.987 101.080 1.00 30.07 6 ATOM 2535 C PHE A 473 30.547 39.904 100.579 1.00 36.31 6 ATOM 2536 O PHE A 473 31.301 40.148 101.525 1.00 36.19 8 ATOM 2537 N ASP A 474 30.676 40.454 99.697 1.00 34.65 7 ATOM 2538 CA ASP A 474 31.473 41.667 99.459 1.00 34.17 6 ATOM 2539 CB ASP A 474 31.238 42.184 98.033 1.00 35.20 6 ATOM 2540 CG ASP A 474 31.670 41.181 96.956 1.00 37.35 6 ATOM 2541 OD1 ASP A 474 32.093 40.050 97.292 1.00 36.56 8 ATOM 2542 OD2 ASP A 474 31.585 41.529 95.761 1.00 37.81 8 ATOM 2543 C ASP A 474 31.339 42.805 100.479 1.00 33.28 6 ATOM 2544 O ASP A 474 30.243 43.070 100.985 1.00 33.00 8 ATOM 2545 N TYR A 475 32.336 43.598 100.600 1.00 32.50 7 ATOM 2546 CA TYR A 475 32.443 44.665 101.607 1.00 30.82 6 ATOM 2547 CB TYR A 475 32.403 44.028 103.011 1.00 29.88 6 ATOM 2548 CG TYR A 475 32.553 44.941 104.222 1.00 27.41 6 ATOM 2549 CD1 TYR A 475 31.516 45.815 104.617 1.00 27.87 6 ATOM 2550 CE1 TYR A 475 31.628 46.597 105.806 1.00 25.76 6 ATOM 2551 CD2 TYR A 475 33.708 44.870 105.032 1.00 27.77 6 ATOM 2552 CE2 TYR A 475 33.829 45.642 106.216 1.00 25.75 6 ATOM 2553 CZ TYR A 475 32.787 46.497 106.593 1.00 25.68 6 ATOM 2554 OH TYR A 475 32.912 47.239 107.744 1.00 25.85 8 ATOM 2555 C TYR A 475 33.718 45.504 101.481 1.00 30.76 6 ATOM 2556 O TYR A 475 34.777 44.998 101.106 1.00 31.24 8 ATOM 2557 N ILE A 476 33.582 46.790 101.809 1.00 31.14 7 ATOM 2558 CA ILE A 476 34.673 47.774 101.836 1.00 31.20 6 ATOM 2559 CB ILE A 476 34.627 48.784 100.628 1.00 32.45 6 ATOM 2560 CG2 ILE A 476 35.685 49.893 100.811 1.00 32.13 6 ATOM 2561 CG1 ILE A 476 34.903 48.060 99.299 1.00 32.62 6 ATOM 2562 CD1 ILE A 476 34.562 48.862 98.049 1.00 34.46 6 ATOM 2563 C ILE A 476 34.438 48.513 103.166 1.00 31.57 6 ATOM 2564 O ILE A 476 33.349 49.053 103.396 1.00 30.47 8 ATOM 2565 N ALA A 477 35.457 48.529 104.028 1.00 32.70 7 ATOM 2566 CA ALA A 477 35.375 49.166 105.349 1.00 34.90 6 ATOM 2567 CB ALA A 477 36.490 48.657 106.248 1.00 34.36 6 ATOM 2568 C ALA A 477 35.329 50.688 105.391 1.00 36.49 6 ATOM 2569 O ALA A 477 35.830 51.365 104.490 1.00 36.95 8 ATOM 2570 N ASP A 478 34.726 51.199 106.465 1.00 38.84 7 ATOM 2571 CA ASP A 478 34.575 52.633 106.717 1.00 41.31 6 ATOM 2572 CB ASP A 478 33.314 52.901 107.564 1.00 42.94 6 ATOM 2573 CG ASP A 478 33.279 52.091 108.862 1.00 44.91 6 ATOM 2574 OD1 ASP A 478 33.181 50.846 108.793 1.00 46.07 8 ATOM 2575 OD2 ASP A 478 33.340 52.704 109.949 1.00 46.21 8 ATOM 2576 C ASP A 478 35.818 53.249 107.376 1.00 42.23 6 ATOM 2577 O ASP A 478 35.977 54.474 107.398 1.00 43.43 8 ATOM 2578 N TRP A 479 36.681 52.385 107.914 1.00 42.38 7 ATOM 2579 CA TRP A 479 37.924 52.797 108.570 1.00 42.14 6 ATOM 2580 CB TRP A 479 38.124 52.045 109.905 1.00 40.95 6 ATOM 2581 CG TRP A 479 38.042 50.527 109.834 1.00 39.18 6 ATOM 2582 CD2 TRP A 479 39.135 49.604 109.696 1.00 38.78 6 ATOM 2583 CE2 TRP A 479 38.577 48.296 109.672 1.00 38.20 6 ATOM 2584 CE3 TRP A 479 40.537 49.751 109.589 1.00 38.36 6 ATOM 2585 CD1 TRP A 479 36.905 49.764 109.891 1.00 38.88 6 ATOM 2586 NE1 TRP A 479 37.218 48.429 109.793 1.00 37.91 7 ATOM 2587 CZ2 TRP A 479 39.373 47.130 109.543 1.00 37.40 6 ATOM 2588 CZ3 TRP A 479 41.339 48.586 109.460 1.00 38.31 6 ATOM 2589 CH2 TRP A 479 40.744 47.292 109.439 1.00 37.72 6 ATOM 2590 C TRP A 479 39.136 52.613 107.653 1.00 42.81 6 ATOM 2591 O TRP A 479 40.153 53.307 107.870 1.00 43.20 8 ATOM 2592 OXT TRP A 479 39.057 51.763 106.739 1.00 42.86 8 ATOM 2593 PG ANP B 500 39.277 25.675 111.120 1.00 11.47 15 ATOM 2594 N3B ANP B 500 40.220 26.675 110.203 1.00 12.92 7 ATOM 2595 O1G ANP B 500 37.828 25.963 110.749 1.00 12.02 8 ATOM 2596 O2G ANP B 500 39.680 26.079 112.480 1.00 11.21 8 ATOM 2597 O3G ANP B 500 39.646 24.294 110.843 1.00 11.94 8 ATOM 2598 PB ANP B 500 39.750 27.681 108.948 1.00 13.36 15 ATOM 2599 O1B ANP B 500 39.861 26.926 107.715 1.00 16.59 8 ATOM 2600 O2B ANP B 500 38.437 28.267 109.261 1.00 14.32 8 ATOM 2601 PA ANP B 500 41.152 30.005 109.978 1.00 13.37 15 ATOM 2602 O1A ANP B 500 40.376 31.217 109.702 1.00 12.08 8 ATOM 2603 O2A ANP B 500 41.090 29.418 111.349 1.00 12.13 8 ATOM 2604 O3A ANP B 500 40.845 28.864 108.875 1.00 13.96 8 ATOM 2605 O5* ANP B 500 42.679 30.329 109.603 1.00 12.57 8 ATOM 2606 C5* ANP B 500 43.688 29.309 109.757 1.00 11.88 6 ATOM 2607 C4* ANP B 500 44.884 29.865 110.493 1.00 11.53 6 ATOM 2608 O4* ANP B 500 45.350 31.080 109.861 1.00 12.10 8 ATOM 2609 C3* ANP B 500 44.566 30.261 111.926 1.00 12.07 6 ATOM 2610 O3* ANP B 500 44.520 29.161 112.830 1.00 12.82 8 ATOM 2611 C2* ANP B 500 45.640 31.288 112.191 1.00 12.45 6 ATOM 2612 O2* ANP B 500 46.871 30.642 112.555 1.00 13.19 8 ATOM 2613 C1* ANP B 500 45.815 32.006 110.863 1.00 12.34 6 ATOM 2614 N9 ANP B 500 45.021 33.246 110.835 1.00 11.84 7 ATOM 2615 C8 ANP B 500 43.652 33.406 110.656 1.00 12.58 6 ATOM 2616 N7 ANP B 500 43.250 34.638 110.689 1.00 12.01 7 ATOM 2617 C5 ANP B 500 44.411 35.359 110.903 1.00 10.84 6 ATOM 2618 C6 ANP B 500 44.659 36.746 111.043 1.00 11.91 6 ATOM 2619 N6 ANP B 500 43.683 37.652 110.977 1.00 11.89 7 ATOM 2620 N1 ANP B 500 45.964 37.150 111.254 1.00 11.05 7 ATOM 2621 C2 ANP B 500 46.942 36.227 111.317 1.00 10.77 6 ATOM 2622 N3 ANP B 500 46.817 34.892 111.198 1.00 10.34 7 ATOM 2623 C4 ANP B 500 45.505 34.525 110.992 1.00 11.09 6 ATOM 2624 MN MN B 501 40.359 28.039 112.697 1.00 11.36 6 ATOM 2625 MN MN B 502 36.921 27.830 110.722 1.00 13.10 6 ATOM 2626 C GLY C 3 50.969 18.410 122.200 1.00 36.86 6 ATOM 2627 O GLY C 3 51.016 19.584 121.817 1.00 38.87 8 ATOM 2628 N GLY C 3 51.781 17.163 124.216 1.00 37.63 7 ATOM 2629 CA GLY C 3 52.156 17.802 122.925 1.00 37.92 6 ATOM 2630 N ARG C 4 49.920 17.598 122.012 1.00 34.55 7 ATOM 2631 CA ARG C 4 48.657 17.957 121.336 1.00 29.66 6 ATOM 2632 CB ARG C 4 47.836 18.940 122.194 1.00 30.31 6 ATOM 2633 CG ARG C 4 46.489 19.447 121.626 1.00 28.23 6 ATOM 2634 CD ARG C 4 46.298 20.867 122.134 1.00 26.41 6 ATOM 2635 NE ARG C 4 45.096 21.613 121.739 1.00 21.02 7 ATOM 2636 CZ ARG C 4 44.791 22.028 120.509 1.00 19.94 6 ATOM 2637 NH1 ARG C 4 45.562 21.747 119.468 1.00 18.31 7 ATOM 2638 NH2 ARG C 4 43.795 22.884 120.345 1.00 22.61 7 ATOM 2639 C ARG C 4 48.792 18.467 119.889 1.00 27.38 6 ATOM 2640 O ARG C 4 49.335 19.553 119.651 1.00 25.67 8 ATOM 2641 N PRO C 5 48.333 17.665 118.902 1.00 23.85 7 ATOM 2642 CD PRO C 5 47.951 16.240 118.995 1.00 24.25 6 ATOM 2643 CA PRO C 5 48.417 18.091 117.497 1.00 21.43 6 ATOM 2644 CB PRO C 5 48.198 16.783 116.729 1.00 23.45 6 ATOM 2645 CG PRO C 5 47.342 15.972 117.647 1.00 24.54 6 ATOM 2646 C PRO C 5 47.356 19.146 117.153 1.00 19.72 6 ATOM 2647 O PRO C 5 46.430 19.378 117.941 1.00 17.72 8 ATOM 2648 N ARG C 6 47.509 19.786 115.993 1.00 18.14 7 ATOM 2649 CA ARG C 6 46.571 20.807 115.514 1.00 18.74 6 ATOM 2650 CB ARG C 6 47.024 21.393 114.181 1.00 19.45 6 ATOM 2651 CG ARG C 6 48.194 22.325 114.272 1.00 22.63 6 ATOM 2652 CD ARG C 6 48.338 23.129 112.992 1.00 22.50 6 ATOM 2653 NE ARG C 6 47.280 24.125 112.790 1.00 22.01 7 ATOM 2654 CZ ARG C 6 47.251 25.335 113.354 1.00 20.10 6 ATOM 2655 NH1 ARG C 6 48.222 25.728 114.172 1.00 20.75 7 ATOM 2656 NH2 ARG C 6 46.246 26.160 113.097 1.00 20.44 7 ATOM 2657 C ARG C 6 45.178 20.227 115.332 1.00 18.25 6 ATOM 2658 O ARG C 6 45.022 19.090 114.881 1.00 19.16 8 ATOM 2659 N THR C 7 44.178 21.010 115.719 1.00 18.37 7 ATOM 2660 CA THR C 7 42.790 20.587 115.628 1.00 18.23 6 ATOM 2661 CB THR C 7 42.073 20.742 116.993 1.00 18.36 6 ATOM 2662 OG1 THR C 7 41.969 22.129 117.346 1.00 22.70 8 ATOM 2663 CG2 THR C 7 42.811 20.000 118.096 1.00 18.61 6 ATOM 2664 C THR C 7 42.039 21.343 114.528 1.00 18.62 6 ATOM 2665 O THR C 7 42.195 22.557 114.375 1.00 19.25 8 ATOM 2666 N THR C 8 41.234 20.607 113.765 1.00 18.24 7 ATOM 2667 CA THR C 8 40.458 21.163 112.657 1.00 17.38 6 ATOM 2668 CB THR C 8 40.724 20.389 111.335 1.00 21.04 6 ATOM 2669 OG1 THR C 8 40.479 18.993 111.541 1.00 25.51 8 ATOM 2670 CG2 THR C 8 42.163 20.580 110.866 1.00 22.39 6 ATOM 2671 C THR C 8 38.959 21.117 112.937 1.00 15.74 6 ATOM 2672 O THR C 8 38.470 20.188 113.586 1.00 14.43 8 ATOM 2673 N SER C 9 38.232 22.101 112.412 1.00 14.11 7 ATOM 2674 CA SER C 9 36.786 22.161 112.589 1.00 15.02 6 ATOM 2675 CB SER C 9 36.275 23.606 112.519 1.00 14.75 6 ATOM 2676 OG SER C 9 36.125 24.060 111.182 1.00 16.19 8 ATOM 2677 C SER C 9 36.048 21.291 111.572 1.00 15.89 6 ATOM 2678 O SER C 9 36.647 20.803 110.605 1.00 17.62 8 ATOM 2679 N PHE C 10 34.758 21.080 111.826 1.00 16.18 7 ATOM 2680 CA PHE C 10 33.890 20.298 110.946 1.00 16.48 6 ATOM 2681 CB PHE C 10 33.878 18.796 111.341 1.00 15.78 6 ATOM 2682 CG PHE C 10 33.088 18.479 112.595 1.00 16.58 6 ATOM 2683 CD1 PHE C 10 31.786 17.932 112.507 1.00 16.68 6 ATOM 2684 CD2 PHE C 10 33.614 18.772 113.866 1.00 16.84 6 ATOM 2685 CE1 PHE C 10 31.015 17.691 113.672 1.00 17.05 6 ATOM 2686 CE2 PHE C 10 32.858 18.536 115.045 1.00 16.94 6 ATOM 2687 CZ PHE C 10 31.556 17.997 114.946 1.00 16.52 6 ATOM 2688 C PHE C 10 32.478 20.878 110.987 1.00 17.20 6 ATOM 2689 O PHE C 10 32.136 21.647 111.890 1.00 15.11 8 ATOM 2690 N ALA C 11 31.659 20.440 110.036 1.00 18.60 7 ATOM 2691 CA ALA C 11 30.262 20.835 109.920 1.00 21.47 6 ATOM 2692 CB ALA C 11 30.123 22.153 109.151 1.00 20.50 6 ATOM 2693 C ALA C 11 29.561 19.709 109.181 1.00 23.32 6 ATOM 2694 O ALA C 11 29.986 19.320 108.090 1.00 25.50 8 ATOM 2695 N GLU C 12 28.527 19.152 109.810 1.00 25.80 7 ATOM 2696 CA GLU C 12 27.743 18.057 109.235 1.00 29.12 6 ATOM 2697 CB GLU C 12 26.939 17.360 110.340 1.00 30.62 6 ATOM 2698 CG GLU C 12 26.281 16.038 109.946 1.00 34.19 6 ATOM 2699 CD GLU C 12 25.518 15.406 111.095 1.00 35.67 6 ATOM 2700 OE1 GLU C 12 24.457 15.948 111.483 1.00 37.03 8 ATOM 2701 OE2 GLU C 12 25.984 14.368 111.615 1.00 37.50 8 ATOM 2702 C GLU C 12 26.811 18.584 108.137 1.00 30.90 6 ATOM 2703 O GLU C 12 26.160 19.629 108.363 1.00 32.72 8 ATOM 2704 OXT GLU C 12 26.772 17.958 107.056 1.00 32.94 8 ATOM 2705 OH2 TIP S 1 50.880 30.829 115.354 1.00 12.37 8 ATOM 2706 OH2 TIP S 2 39.107 18.395 125.671 1.00 13.74 8 ATOM 2707 OH2 TIP S 3 50.067 39.054 125.744 1.00 14.46 8 ATOM 2708 OH2 TIP S 4 33.214 17.947 132.346 1.00 14.31 8 ATOM 2709 OH2 TIP S 5 33.870 23.765 119.066 1.00 12.75 8 ATOM 2710 OH2 TIP S 6 55.058 36.723 114.047 1.00 14.05 8 ATOM 2711 OH2 TIP S 7 35.342 19.387 124.811 1.00 10.52 8 ATOM 2712 OH2 TIP S 8 22.143 27.022 128.885 1.00 15.75 8 ATOM 2713 OH2 TIP S 9 35.369 27.593 112.409 1.00 18.44 8 ATOM 2714 OH2 TIP S 10 34.525 38.856 139.389 1.00 14.38 8 ATOM 2715 OH2 TIP S 11 50.595 23.028 126.483 1.00 21.63 8 ATOM 2716 OH2 TIP S 12 50.109 30.822 138.650 1.00 18.51 8 ATOM 2717 OH2 TIP S 13 48.957 28.883 111.450 1.00 15.57 8 ATOM 2718 OH2 TIP S 14 36.462 44.242 115.382 1.00 16.52 8 ATOM 2719 OH2 TIP S 15 39.815 33.856 109.902 1.00 17.16 8 ATOM 2720 OH2 TIP S 16 35.195 41.517 138.199 1.00 15.86 8 ATOM 2721 OH2 TIP S 17 35.202 42.427 113.616 1.00 19.42 8 ATOM 2722 OH2 TIP S 18 33.376 30.532 114.196 1.00 16.90 8 ATOM 2723 OH2 TIP S 19 22.792 38.265 114.873 1.00 15.62 8 ATOM 2724 OH2 TIP S 20 43.567 40.244 113.918 1.00 16.93 8 ATOM 2725 OH2 TIP S 21 20.810 30.568 123.500 1.00 17.32 8 ATOM 2726 OH2 TIP S 22 41.060 37.798 140.335 1.00 14.56 8 ATOM 2727 OH2 TIP S 23 35.177 46.194 109.346 1.00 21.19 8 ATOM 2728 OH2 TIP S 24 29.447 18.326 135.228 1.00 16.88 8 ATOM 2729 OH2 TIP S 25 30.561 22.975 121.268 1.00 16.64 8 ATOM 2730 OH2 TIP S 26 22.413 18.170 127.955 1.00 14.88 8 ATOM 2731 OH2 TIP S 27 46.214 17.759 125.315 1.00 19.36 8 ATOM 2732 OH2 TIP S 28 19.322 20.943 134.518 1.00 22.03 8 ATOM 2733 OH2 TIP S 29 44.096 32.795 140.620 1.00 23.66 8 ATOM 2734 OH2 TIP S 30 30.206 23.891 118.727 1.00 16.83 8 ATOM 2735 OH2 TIP S 31 32.936 27.738 121.244 1.00 15.40 8 ATOM 2736 OH2 TIP S 32 58.831 31.975 120.394 1.00 18.83 8 ATOM 2737 OH2 TIP S 33 48.566 43.482 115.194 1.00 23.92 8 ATOM 2738 OH2 TIP S 34 40.844 15.752 133.043 1.00 16.61 8 ATOM 2739 OH2 TIP S 35 35.070 43.968 111.120 1.00 17.04 8 ATOM 2740 OH2 TIP S 36 25.259 15.523 128.677 1.00 17.49 8 ATOM 2741 OH2 TIP S 37 28.852 33.859 139.017 1.00 21.63 8 ATOM 2742 OH2 TIP S 38 52.813 32.605 131.982 1.00 17.25 8 ATOM 2743 OH2 TIP S 39 43.349 9.991 135.666 1.00 16.46 8 ATOM 2744 OH2 TIP S 40 48.644 27.596 135.872 1.00 18.69 8 ATOM 2745 OH2 TIP S 41 51.757 46.157 124.741 1.00 19.06 8 ATOM 2746 OH2 TIP S 42 16.342 18.660 124.021 1.00 25.31 8 ATOM 2747 OH2 TIP S 43 35.925 29.248 107.006 1.00 18.94 8 ATOM 2748 OH2 TIP S 44 26.605 13.506 129.590 1.00 20.83 8 ATOM 2749 OH2 TIP S 45 46.526 44.521 109.624 1.00 21.14 8 ATOM 2750 OH2 TIP S 46 59.862 25.385 124.398 1.00 21.24 8 ATOM 2751 OH2 TIP S 47 36.431 24.738 118.944 1.00 12.45 8 ATOM 2752 OH2 TIP S 48 24.275 25.017 125.190 1.00 16.82 8 ATOM 2753 OH2 TIP S 49 26.549 18.879 134.765 1.00 17.15 8 ATOM 2754 OH2 TIP S 50 46.910 22.255 124.892 1.00 19.18 8 ATOM 2755 OH2 TIP S 51 23.048 12.045 127.642 1.00 15.85 8 ATOM 2756 OH2 TIP S 52 46.279 46.528 120.576 1.00 26.09 8 ATOM 2757 OH2 TIP S 53 48.088 19.125 134.329 1.00 19.71 8 ATOM 2758 OH2 TIP S 54 41.201 15.894 140.167 1.00 19.37 8 ATOM 2759 OH2 TIP S 55 32.532 32.821 142.399 1.00 18.79 8 ATOM 2760 OH2 TIP S 56 41.005 13.422 118.526 1.00 22.94 8 ATOM 2761 OH2 TIP S 57 45.423 42.293 114.849 1.00 21.91 8 ATOM 2762 OH2 TIP S 58 34.171 45.681 136.533 1.00 18.22 8 ATOM 2763 OH2 TIP S 59 59.549 36.211 122.042 1.00 21.68 8 ATOM 2764 OH2 TIP S 60 41.715 23.526 109.597 1.00 26.86 8 ATOM 2765 OH2 TIP S 61 59.408 32.626 117.755 1.00 22.58 8 ATOM 2766 OH2 TIP S 62 28.363 12.355 132.625 1.00 21.09 8 ATOM 2767 OH2 TIP S 63 48.570 27.462 139.496 1.00 40.67 8 ATOM 2768 OH2 TIP S 64 14.679 33.201 125.048 1.00 28.70 8 ATOM 2769 OH2 TIP S 65 36.643 6.730 125.886 1.00 28.64 8 ATOM 2770 OH2 TIP S 66 51.055 28.844 113.326 1.00 15.46 8 ATOM 2771 OH2 TIP S 67 32.935 24.342 121.669 1.00 22.64 8 ATOM 2772 OH2 TIP S 68 41.626 12.464 128.484 1.00 19.34 8 ATOM 2773 OH2 TIP S 69 23.321 32.418 110.820 1.00 23.93 8 ATOM 2774 OH2 TIP S 70 36.942 34.509 109.717 1.00 16.36 8 ATOM 2775 OH2 TIP S 71 20.536 26.082 113.618 1.00 19.58 8 ATOM 2776 OH2 TIP S 72 44.163 40.980 137.433 1.00 26.23 8 ATOM 2777 OH2 TIP S 73 22.941 35.738 122.535 1.00 21.61 8 ATOM 2778 OH2 TIP S 74 40.478 18.154 115.439 1.00 20.64 8 ATOM 2779 OH2 TIP S 75 32.178 43.404 125.578 1.00 27.41 8 ATOM 2780 OH2 TIP S 76 21.320 38.314 122.781 1.00 34.21 8 ATOM 2781 OH2 TIP S 77 43.735 15.060 128.317 1.00 20.40 8 ATOM 2782 OH2 TIP S 78 47.445 26.751 110.123 1.00 20.45 8 ATOM 2783 OH2 TIP S 79 21.787 24.231 125.522 1.00 22.05 8 ATOM 2784 OH2 TIP S 80 41.670 44.807 136.137 1.00 23.57 8 ATOM 2785 OH2 TIP S 81 58.366 30.315 114.316 1.00 20.06 8 ATOM 2786 OH2 TIP S 82 29.673 9.405 133.896 1.00 31.61 8 ATOM 2787 OH2 TIP S 83 24.775 17.987 129.036 1.00 25.02 8 ATOM 2788 OH2 TIP S 84 46.614 13.440 131.186 1.00 26.06 8 ATOM 2789 OH2 TIP S 85 23.993 39.811 112.790 1.00 34.34 8 ATOM 2790 OH2 TIP S 86 47.303 47.864 126.679 1.00 24.99 8 ATOM 2791 OH2 TIP S 87 53.966 43.943 128.012 1.00 28.55 8 ATOM 2792 OH2 TIP S 88 47.858 23.095 127.099 1.00 22.71 8 ATOM 2793 OH2 TIP S 89 57.786 30.944 110.897 1.00 26.75 8 ATOM 2794 OH2 TIP S 90 39.820 35.599 143.781 1.00 31.44 8 ATOM 2795 OH2 TIP S 91 49.597 33.870 138.671 1.00 22.65 8 ATOM 2796 OH2 TIP S 92 26.763 22.386 107.816 1.00 29.29 8 ATOM 2797 OH2 TIP S 93 42.793 25.932 109.453 1.00 24.89 8 ATOM 2798 OH2 TIP S 94 38.530 11.440 135.902 1.00 27.54 8 ATOM 2799 OH2 TIP S 95 50.004 19.487 126.432 1.00 23.31 8 ATOM 2800 OH2 TIP S 96 43.449 8.768 137.925 1.00 25.25 8 ATOM 2801 OH2 TIP S 97 24.084 36.713 137.240 1.00 32.63 8 ATOM 2802 OH2 TIP S 98 52.169 36.019 135.556 1.00 25.64 8 ATOM 2803 OH2 TIP S 99 54.397 30.590 131.474 1.00 25.34 8 ATOM 2804 OH2 TIP S 100 42.190 47.366 136.555 1.00 28.23 8 ATOM 2805 OH2 TIP S 101 46.582 48.347 96.082 1.00 26.23 8 ATOM 2806 OH2 TIP S 102 28.878 47.284 117.243 1.00 29.18 8 ATOM 2807 OH2 TIP S 103 41.841 4.408 123.418 1.00 38.41 8 ATOM 2808 OH2 TIP S 104 19.590 29.610 130.555 1.00 28.07 8 ATOM 2809 OH2 TIP S 105 37.559 25.439 144.575 1.00 23.58 8 ATOM 2810 OH2 TIP S 106 52.351 47.830 122.793 1.00 26.71 8 ATOM 2811 OH2 TIP S 107 27.772 11.423 120.729 1.00 27.59 8 ATOM 2812 OH2 TIP S 108 37.304 17.824 112.284 1.00 29.31 8 ATOM 2813 OH2 TIP S 109 25.896 40.003 125.964 1.00 44.52 8 ATOM 2814 OH2 TIP S 110 55.255 30.966 102.843 1.00 22.19 8 ATOM 2815 OH2 TIP S 111 54.120 25.349 117.852 1.00 30.54 8 ATOM 2816 OH2 TIP S 112 31.410 8.275 120.685 1.00 24.19 8 ATOM 2817 OH2 TIP S 113 33.439 16.859 134.908 1.00 23.68 8 ATOM 2818 OH2 TIP S 115 26.440 26.129 105.300 1.00 30.80 8 ATOM 2819 OH2 TIP S 116 55.443 26.741 119.663 1.00 22.09 8 ATOM 2820 OH2 TIP S 117 54.494 45.049 93.866 1.00 42.51 8 ATOM 2821 OH2 TIP S 118 40.757 52.771 134.950 1.00 37.87 8 ATOM 2822 OH2 TIP S 119 41.165 7.640 126.430 1.00 23.76 8 ATOM 2823 OH2 TIP S 120 65.214 39.814 115.057 1.00 29.22 8 ATOM 2824 OH2 TIP S 121 50.394 47.451 108.308 1.00 30.19 8 ATOM 2825 OH2 TIP S 122 33.739 23.776 109.559 1.00 28.48 8 ATOM 2826 OH2 TIP S 123 33.200 19.214 107.711 1.00 32.65 8 ATOM 2827 OH2 TIP S 124 16.774 32.211 116.325 1.00 23.24 8 ATOM 2828 OH2 TIP S 125 49.654 18.866 114.313 1.00 34.58 8 ATOM 2829 OH2 TIP S 126 19.542 22.338 128.436 1.00 25.45 8 ATOM 2830 OH2 TIP S 127 43.183 15.839 106.195 1.00 48.46 8 ATOM 2831 OH2 TIP S 128 43.972 16.480 117.930 1.00 37.24 8 ATOM 2832 OH2 TIP S 129 32.264 25.802 140.311 1.00 31.72 8 ATOM 2833 OH2 TIP S 130 58.409 39.864 124.999 1.00 27.79 8 ATOM 2834 OH2 TIP S 131 50.717 27.447 116.398 1.00 28.18 8 ATOM 2835 OH2 TIP S 132 54.524 34.273 124.961 1.00 27.62 8 ATOM 2836 OH2 TIP S 133 44.942 8.806 122.076 1.00 23.21 8 ATOM 2837 OH2 TIP S 134 45.019 49.937 103.549 1.00 35.77 8 ATOM 2838 OH2 TIP S 135 13.939 35.763 126.601 1.00 28.79 8 ATOM 2839 OH2 TIP S 136 47.697 45.857 133.970 1.00 31.82 8 ATOM 2840 OH2 TIP S 137 42.951 5.634 120.810 1.00 40.74 8 ATOM 2841 OH2 TIP S 138 24.811 25.975 102.769 1.00 42.30 8 ATOM 2842 OH2 TIP S 139 19.404 27.466 134.148 1.00 35.78 8 ATOM 2843 OH2 TIP S 140 19.722 16.378 115.953 1.00 38.31 8 ATOM 2844 OH2 TIP S 141 33.165 26.435 108.761 1.00 25.71 8 ATOM 2845 OH2 TIP S 142 23.994 32.686 105.786 1.00 32.48 8 ATOM 2846 OH2 TIP S 143 56.731 31.921 100.637 1.00 44.83 8 ATOM 2847 OH2 TIP S 144 23.408 39.422 130.554 1.00 36.14 8 ATOM 2848 OH2 TIP S 145 16.404 27.543 125.268 1.00 23.35 8 ATOM 2849 OH2 TIP S 146 21.913 33.905 135.058 1.00 26.19 8 ATOM 2850 OH2 TIP S 147 24.038 19.019 111.497 1.00 22.27 8 ATOM 2851 OH2 TIP S 148 45.060 11.433 142.503 1.00 23.88 8 ATOM 2852 OH2 TIP S 149 41.063 15.170 115.913 1.00 31.28 8 ATOM 2853 OH2 TIP S 150 21.752 18.570 116.211 1.00 24.20 8 ATOM 2854 OH2 TIP S 151 59.501 33.631 122.358 1.00 46.23 8 ATOM 2855 OH2 TIP S 152 58.126 27.185 113.944 1.00 36.35 8 ATOM 2856 OH2 TIP S 153 20.938 13.871 115.607 1.00 46.26 8 ATOM 2857 OH2 TIP S 154 29.637 44.495 124.570 1.00 36.62 8 ATOM 2858 OH2 TIP S 155 43.366 24.704 113.048 1.00 25.36 8 ATOM 2859 OH2 TIP S 156 35.452 16.596 138.403 1.00 42.24 8 ATOM 2860 OH2 TIP S 157 48.297 23.939 137.060 1.00 36.41 8 ATOM 2861 OH2 TIP S 158 19.303 28.323 114.801 1.00 26.83 8 ATOM 2862 OH2 TIP S 159 63.482 40.278 122.101 1.00 35.37 8 ATOM 2863 OH2 TIP S 160 14.100 24.011 122.138 1.00 36.60 8 ATOM 2864 OH2 TIP S 161 32.521 20.362 136.350 1.00 28.69 8 ATOM 2865 OH2 TIP S 162 54.331 38.297 132.253 1.00 40.29 8 ATOM 2866 OH2 TIP S 163 33.286 30.321 143.348 1.00 43.86 8 ATOM 2867 OH2 TIP S 164 14.833 20.433 122.703 1.00 48.23 8 ATOM 2868 OH2 TIP S 165 17.109 25.312 116.582 1.00 48.74 8 ATOM 2869 OH2 TIP S 166 36.837 27.153 93.119 1.00 30.29 8 ATOM 2870 OH2 TIP S 167 23.606 31.494 128.416 1.00 20.96 8 ATOM 2871 OH2 TIP S 168 42.297 12.908 116.241 1.00 26.12 8 ATOM 2872 OH2 TIP S 169 38.988 47.325 90.105 1.00 56.33 8 ATOM 2873 OH2 TIP S 170 49.907 40.412 92.821 1.00 38.05 8 ATOM 2874 OH2 TIP S 171 42.725 43.422 129.053 1.00 27.81 8 ATOM 2875 OH2 TIP S 172 25.859 45.309 121.544 1.00 32.71 8 ATOM 2876 OH2 TIP S 173 43.657 16.641 114.719 1.00 37.51 8 ATOM 2877 OH2 TIP S 174 57.561 27.727 130.474 1.00 42.17 8 ATOM 2878 OH2 TIP S 175 25.852 44.022 101.193 1.00 52.15 8 ATOM 2879 OH2 TIP S 176 17.889 41.128 118.915 1.00 31.81 8 ATOM 2880 OH2 TIP S 177 54.917 44.291 118.312 1.00 33.01 8 ATOM 2881 OH2 TIP S 178 45.757 32.304 144.442 1.00 38.19 8 ATOM 2882 OH2 TIP S 179 45.113 45.502 117.334 1.00 33.86 8 ATOM 2883 OH2 TIP S 180 59.492 31.846 104.520 1.00 47.26 8 ATOM 2884 OH2 TIP S 181 25.260 25.416 100.117 1.00 33.58 8 ATOM 2885 OH2 TIP S 182 38.607 14.869 139.608 1.00 34.71 8 ATOM 2886 OH2 TIP S 183 22.591 26.885 126.261 1.00 33.31 8 ATOM 2887 OH2 TIP S 184 59.021 33.013 110.018 1.00 28.53 8 ATOM 2888 OH2 TIP S 185 43.038 45.888 128.862 1.00 40.36 8 ATOM 2889 OH2 TIP S 186 47.941 12.202 119.338 1.00 37.77 8 ATOM 2890 OH2 TIP S 187 43.234 43.410 120.437 1.00 36.29 8 ATOM 2891 OH2 TIP S 188 39.225 54.856 126.747 1.00 44.07 8 ATOM 2892 OH2 TIP S 189 55.049 40.893 112.016 1.00 27.70 8 ATOM 2893 OH2 TIP S 190 42.257 23.718 146.369 1.00 39.05 8 ATOM 2894 OH2 TIP S 191 53.943 21.613 124.180 1.00 49.22 8 ATOM 2895 OH2 TIP S 192 56.224 33.476 96.599 1.00 53.68 8 ATOM 2896 OH2 TIP S 193 30.824 12.457 134.462 1.00 32.58 8 ATOM 2897 OH2 TIP S 194 23.554 29.013 108.913 1.00 38.73 8 ATOM 2898 OH2 TIP S 195 44.443 14.105 117.031 1.00 35.65 8 ATOM 2899 OH2 TIP S 196 59.973 36.155 109.502 1.00 31.57 8 ATOM 2900 OH2 TIP S 197 41.011 55.319 134.060 1.00 36.62 8 ATOM 2901 OH2 TIP S 198 45.295 48.877 108.403 1.00 38.36 8 ATOM 2902 OH2 TIP S 199 47.416 43.146 132.946 1.00 31.64 8 ATOM 2903 OH2 TIP S 200 24.051 28.088 135.556 1.00 43.17 8 ATOM 2904 OH2 TIP S 201 16.831 22.525 127.492 1.00 48.22 8 ATOM 2905 OH2 TIP S 202 48.284 44.483 111.583 1.00 36.56 8 ATOM 2906 OH2 TIP S 203 60.725 47.338 110.308 1.00 49.82 8 ATOM 2907 OH2 TIP S 204 43.100 52.688 126.865 1.00 31.41 8 ATOM 2908 OH2 TIP S 205 50.321 22.195 105.582 1.00 38.95 8 ATOM 2909 OH2 TIP S 206 42.601 41.435 130.811 1.00 22.01 8 ATOM 2910 OH2 TIP S 207 51.144 42.594 132.911 1.00 36.01 8 ATOM 2911 OH2 TIP S 208 44.036 24.667 101.832 1.00 33.33 8 ATOM 2912 OH2 TIP S 209 42.693 27.656 107.080 1.00 39.35 8 ATOM 2913 OH2 TIP S 210 42.399 27.193 113.033 1.00 12.71 8 ATOM 2914 OH2 TIP S 211 43.784 17.104 135.439 1.00 69.38 8 ATOM 2915 OH2 TIP S 213 35.386 27.677 109.183 1.00 13.10 8 ATOM 2916 OH2 TIP S 214 56.955 40.837 126.919 1.00 19.43 8 ATOM 2917 OH2 TIP S 215 47.946 14.090 128.896 1.00 18.54 8 ATOM 2918 OH2 TIP S 216 53.846 46.419 126.577 1.00 23.30 8 ATOM 2919 OH2 TIP S 217 19.952 20.857 130.513 1.00 19.78 8 ATOM 2920 OH2 TIP S 218 40.238 13.147 133.257 1.00 19.07 8 ATOM 2921 OH2 TIP S 219 56.395 43.468 127.546 1.00 21.04 8 ATOM 2922 OH2 TIP S 220 20.558 18.224 129.875 1.00 26.18 8 ATOM 2923 OH2 TIP S 221 20.422 25.115 127.685 1.00 21.85 8 ATOM 2924 OH2 TIP S 222 14.184 31.110 126.427 1.00 28.26 8 ATOM 2925 OH2 TIP S 223 25.553 30.355 110.019 1.00 31.91 8 ATOM 2926 OH2 TIP S 224 47.967 19.947 125.134 1.00 32.19 8 ATOM 2927 OH2 TIP S 225 34.508 43.980 128.863 1.00 22.01 8 ATOM 2928 OH2 TIP S 226 27.521 14.466 134.084 1.00 27.11 8 ATOM 2929 OH2 TIP S 227 21.413 32.875 128.511 1.00 33.82 8 ATOM 2930 OH2 TIP S 228 45.964 14.452 127.083 1.00 22.84 8 ATOM 2931 OH2 TIP S 229 38.587 23.359 108.667 1.00 29.48 8 ATOM 2932 OH2 TIP S 230 20.269 29.207 125.913 1.00 23.24 8 ATOM 2933 OH2 TIP S 231 39.823 12.495 130.497 1.00 25.20 8 ATOM 2934 OH2 TIP S 232 49.950 47.945 125.518 1.00 27.81 8 ATOM 2935 OH2 TIP S 233 32.241 25.732 106.303 1.00 29.22 8 ATOM 2936 OH2 TIP S 234 33.109 40.481 141.226 1.00 29.30 8 ATOM 2937 OH2 TIP S 235 59.831 33.318 107.241 1.00 34.80 8 ATOM 2938 OH2 TIP S 236 28.593 29.974 110.014 1.00 32.06 8 ATOM 2939 OH2 TIP S 237 38.866 9.581 114.598 1.00 33.34 8 ATOM 2940 OH2 TIP S 238 30.617 42.655 135.242 1.00 25.00 8 ATOM 2941 OH2 TIP S 239 59.580 29.369 119.157 1.00 27.41 8 ATOM 2942 OH2 TIP S 240 59.263 25.840 127.994 1.00 25.25 8 ATOM 2943 OH2 TIP S 241 52.945 38.826 95.122 1.00 27.00 8 ATOM 2944 OH2 TIP S 242 55.237 48.817 124.217 1.00 26.92 8 ATOM 2945 OH2 TIP S 243 43.729 13.168 130.273 1.00 32.02 8 ATOM 2946 OH2 TIP S 244 30.123 32.187 140.939 1.00 25.60 8 ATOM 2947 OH2 TIP S 245 40.026 24.418 106.879 1.00 32.07 8 ATOM 2948 OH2 TIP S 246 44.986 26.182 110.602 1.00 36.48 8 ATOM 2949 OH2 TIP S 247 43.974 42.983 135.775 1.00 27.66 8 ATOM 2950 OH2 TIP S 248 32.476 29.429 106.822 1.00 22.50 8 ATOM 2951 OH2 TIP S 249 49.297 23.815 123.885 1.00 33.22 8 ATOM 2952 OH2 TIP S 250 31.555 14.849 135.554 1.00 24.45 8 ATOM 2953 OH2 TIP S 251 21.164 41.884 123.013 1.00 35.98 8 ATOM 2954 OH2 TIP S 252 30.843 47.804 101.581 1.00 40.37 8 ATOM 2955 OH2 TIP S 253 48.846 24.693 139.460 1.00 38.73 8 ATOM 2956 OH2 TIP S 254 36.031 45.307 139.275 1.00 41.57 8 ATOM 2957 OH2 TIP S 255 49.287 17.017 125.960 1.00 37.89 8 ATOM 2958 OH2 TIP S 256 28.702 11.672 117.912 1.00 30.33 8 ATOM 2959 OH2 TIP S 257 51.748 20.975 140.597 1.00 27.03 8 ATOM 2960 OH2 TIP S 258 46.406 48.925 93.500 1.00 32.89 8 ATOM 2961 OH2 TIP S 259 26.931 31.784 138.867 1.00 35.58 8 ATOM 2962 OH2 TIP S 260 23.147 38.768 125.295 1.00 34.84 8 ATOM 2963 OH2 TIP S 261 21.971 38.619 128.509 1.00 34.67 8 ATOM 2964 OH2 TIP S 262 34.139 41.177 94.519 1.00 37.52 8 ATOM 2965 OH2 TIP S 263 24.536 35.763 99.936 1.00 40.69 8 ATOM 2966 OH2 TIP S 264 46.648 34.643 140.895 1.00 36.62 8 ATOM 2967 OH2 TIP S 265 56.673 43.421 102.042 1.00 43.17 8 ATOM 2968 OH2 TIP S 266 16.604 34.485 118.429 1.00 41.38 8 ATOM 2969 OH2 TIP S 267 16.849 11.405 119.353 1.00 34.22 8 ATOM 2970 OH2 TIP S 268 32.549 26.181 143.073 1.00 44.93 8 ATOM 2971 OH2 TIP S 269 22.593 29.195 127.173 1.00 32.06 8 ATOM 2972 OH2 TIP S 270 18.527 29.991 113.097 1.00 37.88 8 ATOM 2973 OH2 TIP S 271 56.381 24.501 120.743 1.00 27.28 8 ATOM 2974 OH2 TIP S 272 32.309 45.003 127.570 1.00 29.32 8 ATOM 2975 OH2 TIP S 273 37.897 27.898 105.998 1.00 33.92 8 ATOM 2976 OH2 TIP S 274 51.649 24.974 118.398 1.00 32.10 8 ATOM 2977 OH2 TIP S 275 43.735 5.648 125.168 1.00 44.93 8 ATOM 2978 OH2 TIP S 276 29.348 47.316 108.710 1.00 36.21 8 ATOM 2979 OH2 TIP S 277 30.688 49.378 107.456 1.00 43.40 8 ATOM 2980 OH2 TIP S 278 44.190 41.312 133.446 1.00 37.19 8 ATOM 2981 OH2 TIP S 279 45.682 39.402 134.669 1.00 33.11 8 ATOM 2982 OH2 TIP S 280 27.613 45.102 127.615 1.00 32.73 8 ATOM 2983 OH2 TIP S 281 58.132 26.991 119.962 1.00 29.41 8 ATOM 2984 OH2 TIP S 282 45.720 42.763 139.513 1.00 40.70 8 ATOM 2985 OH2 TIP S 283 39.576 49.576 123.148 1.00 35.95 8 ATOM 2986 OH2 TIP S 284 30.969 22.695 92.932 1.00 43.04 8 ATOM 2987 OH2 TIP S 285 46.919 18.071 112.722 1.00 39.35 8 ATOM 2988 OH2 TIP S 286 47.798 22.226 107.118 1.00 30.08 8 ATOM 2989 OH2 TIP S 287 55.892 43.637 99.492 1.00 48.19 8 ATOM 2990 OH2 TIP S 288 44.818 13.801 149.041 1.00 34.64 8 ATOM 2991 OH2 TIP S 289 45.690 24.705 145.588 1.00 39.19 8 ATOM 2992 OH2 TIP S 290 29.176 15.761 135.675 1.00 34.51 8 ATOM 2993 OH2 TIP S 291 42.825 17.643 112.304 1.00 37.92 8 ATOM 2994 OH2 TIP S 292 56.706 34.093 129.181 1.00 46.18 8 ATOM 2995 OH2 TIP S 293 37.232 47.010 115.324 1.00 34.68 8 ATOM 2996 OH2 TIP S 294 53.675 47.477 93.914 1.00 32.38 8 ATOM 2997 OH2 TIP S 295 19.763 34.206 136.826 1.00 38.33 8 ATOM 2998 OH2 TIP S 296 48.090 21.156 109.806 1.00 35.72 8 ATOM 2999 OH2 TIP S 297 54.401 49.127 99.504 1.00 53.52 8 ATOM 3000 OH2 TIP S 298 39.339 16.696 113.476 1.00 34.62 8 ATOM 3001 OH2 TIP S 299 46.363 25.745 92.992 1.00 43.72 8 ATOM 3002 OH2 TIP S 300 44.035 49.136 96.848 1.00 38.90 8 ATOM 3003 OH2 TIP S 301 49.759 27.583 142.859 1.00 42.94 8 ATOM 3004 OH2 TIP S 302 39.048 23.411 145.575 1.00 32.22 8 ATOM 3005 OH2 TIP S 303 24.979 21.235 139.742 1.00 47.17 8 ATOM 3006 OH2 TIP S 304 38.439 56.154 107.391 1.00 53.30 8 ATOM 3007 OH2 TIP S 305 34.702 19.403 138.510 1.00 32.49 8 ATOM 3008 OH2 TIP S 306 32.195 35.836 90.821 1.00 42.84 8 ATOM 3009 OH2 TIP S 307 63.629 44.256 123.589 1.00 52.83 8 ATOM 3010 OH2 TIP S 308 21.496 42.773 118.806 1.00 45.13 8 ATOM 3011 OH2 TIP S 309 51.157 38.180 134.410 1.00 39.12 8 ATOM 3012 OH2 TIP S 310 55.561 36.748 129.254 1.00 40.55 8 ATOM 3013 OH2 TIP S 311 47.486 47.348 108.619 1.00 39.39 8 ATOM 3014 OH2 TIP S 312 42.392 28.477 99.281 1.00 30.05 8 ATOM 3015 OH2 TIP S 313 34.981 55.570 128.380 1.00 38.28 8 ATOM 3016 OH2 TIP S 314 55.899 46.231 113.430 1.00 41.35 8 ATOM 3017 OH2 TIP S 315 43.370 52.122 103.406 1.00 47.31 8 ATOM 3018 OH2 TIP S 316 26.984 47.057 119.691 1.00 43.80 8 ATOM 3019 OH2 TIP S 317 52.396 29.647 138.706 1.00 43.39 8 ATOM 3020 OH2 TIP S 318 56.619 23.277 112.370 1.00 41.03 8 ATOM 3021 OH2 TIP S 319 55.762 22.376 105.532 1.00 37.46 8 ATOM 3022 OH2 TIP S 320 28.148 40.281 141.592 1.00 42.50 8 ATOM 3023 OH2 TIP S 321 18.613 43.026 120.556 1.00 45.12 8 ATOM 3024 OH2 TIP S 322 58.935 25.489 99.979 1.00 35.77 8 ATOM 3025 OH2 TIP S 323 40.571 50.534 137.662 1.00 41.60 8 ATOM 3026 OH2 TIP S 324 52.014 20.946 125.658 1.00 42.85 8 ATOM 3027 OH2 TIP S 325 42.716 25.829 99.683 1.00 39.82 8 ATOM 3028 OH2 TIP S 326 19.893 24.784 110.667 1.00 35.82 8 ATOM 3029 OH2 TIP S 327 20.960 18.912 112.950 1.00 35.82 8 ATOM 3030 OH2 TIP S 328 51.945 35.676 138.441 1.00 41.14 8 ATOM 3031 OH2 TIP S 329 37.775 52.025 132.407 1.00 40.29 8 ATOM 3032 OH2 TIP S 330 30.493 5.711 121.390 1.00 32.58 8 ATOM 3033 OH2 TIP S 331 16.945 22.758 124.490 1.00 46.50 8 ATOM 3034 OH2 TIP S 332 49.826 20.361 111.604 1.00 43.19 8 ATOM 3035 OH2 TIP S 333 61.140 33.733 111.468 1.00 31.34 8 ATOM 3036 OH2 TIP S 334 47.699 41.062 134.499 1.00 43.66 8 ATOM 3037 OH2 TIP S 335 33.755 41.733 91.691 1.00 53.22 8 ATOM 3038 OH2 TIP S 336 26.364 36.964 138.656 1.00 34.77 8 ATOM 3039 OH2 TIP S 337 52.195 19.821 118.003 1.00 49.79 8 ATOM 3040 OH2 TIP S 338 45.378 39.208 140.928 1.00 44.24 8 ATOM 3041 OH2 TIP S 339 30.964 48.467 118.838 1.00 40.61 8 ATOM 3042 OH2 TIP S 340 41.460 53.913 110.250 1.00 44.09 8 ATOM 3043 OH2 TIP S 341 46.788 21.233 147.348 1.00 41.72 8 ATOM 3044 OH2 TIP S 342 22.262 38.333 138.418 1.00 49.15 8 ATOM 3045 OH2 TIP S 343 18.936 28.397 110.149 1.00 45.05 8 ATOM 3046 OH2 TIP S 344 41.359 3.502 120.430 1.00 39.49 8 ATOM 3047 OH2 TIP S 345 42.638 37.542 142.479 1.00 38.82 8 ATOM 3048 OH2 TIP S 346 19.381 32.382 112.620 1.00 37.75 8 ATOM 3049 OH2 TIP S 347 35.543 24.103 143.337 1.00 38.25 8 ATOM 3050 OH2 TIP S 348 17.914 20.835 132.016 1.00 31.74 8 ATOM 3051 OH2 TIP S 349 50.858 24.159 114.717 1.00 30.33 8 ATOM 3052 OH2 TIP S 350 25.663 38.315 127.729 1.00 33.90 8 ATOM 3053 OH2 TIP S 351 62.530 33.961 113.530 1.00 39.16 8 ATOM 3054 OH2 TIP S 352 49.868 55.189 96.937 1.00 36.35 8 ATOM 3055 OH2 TIP S 353 33.170 27.813 104.969 1.00 32.28 8 ATOM 3056 OH2 TIP S 354 27.775 19.637 104.463 1.00 40.73 8 ATOM 3057 OH2 TIP S 355 41.682 54.782 127.482 1.00 36.10 8 ATOM 3058 OH2 TIP S 356 16.595 29.666 117.069 1.00 30.62 8 ATOM 3059 OH2 TIP S 357 59.680 28.085 115.825 1.00 37.77 8 ATOM 3060 OH2 TIP S 358 32.836 42.032 129.432 1.00 40.02 8 ATOM 3061 OH2 TIP S 359 41.357 38.823 90.291 1.00 43.92 8 ATOM 3062 OH2 TIP S 360 30.971 29.187 141.043 1.00 36.54 8 ATOM 3063 OH2 TIP S 361 19.713 30.822 128.240 1.00 45.66 8 ATOM 3064 OH2 TIP S 362 53.174 47.822 91.393 1.00 40.02 8 ATOM 3065 OH2 TIP S 363 22.473 29.992 136.645 1.00 44.49 8 ATOM 3066 OH2 TIP S 364 23.373 26.355 108.348 1.00 42.18 8 ATOM 3067 OH2 TIP S 365 27.229 45.249 105.988 1.00 38.32 8 ATOM 3068 OH2 TIP S 366 48.848 39.125 133.258 1.00 37.04 8 ATOM 3069 OH2 TIP S 367 44.858 46.631 109.978 1.00 42.07 8 ATOM 3070 OH2 TIP S 368 33.891 37.873 90.331 1.00 39.10 8 ATOM 3071 OH2 TIP S 369 29.187 8.473 124.559 1.00 37.63 8 ATOM 3072 OH2 TIP S 370 46.367 17.893 147.746 1.00 40.65 8 ATOM 3073 OH2 TIP S 371 15.377 9.348 119.481 1.00 42.47 8 ATOM 3074 OH2 TIP S 372 36.325 25.547 107.362 1.00 36.43 8 ATOM 3075 OH2 TIP S 373 61.878 36.279 112.169 1.00 36.00 8 ATOM 3076 OH2 TIP S 374 43.865 29.249 96.871 1.00 37.51 8 ATOM 3077 OH2 TIP S 375 56.790 25.252 115.334 1.00 36.46 8 ATOM 3078 OH2 TIP S 376 26.075 42.793 105.991 1.00 39.92 8 ATOM 3079 OH2 TIP S 377 39.040 5.988 126.942 1.00 49.70 8 ATOM 3080 OH2 TIP S 378 60.599 30.306 112.774 1.00 42.51 8 ATOM 3081 OH2 TIP S 379 19.976 29.184 136.540 1.00 39.69 8 ATOM 3082 OH2 TIP S 380 33.867 23.699 105.007 1.00 39.72 8 ATOM 3083 OH2 TIP S 381 44.042 47.505 112.354 1.00 37.26 8 ATOM 3084 OH2 TIP S 382 39.882 57.673 134.187 1.00 49.20 8 ATOM 3085 OH2 TIP S 383 25.014 26.001 138.981 1.00 37.95 8 ATOM 3086 OH2 TIP S 384 31.577 47.522 127.034 1.00 43.68 8 ATOM 3087 OH2 TIP S 385 30.552 23.935 139.612 1.00 43.84 8 ATOM 3088 OH2 TIP S 386 31.270 8.957 117.782 1.00 41.30 8 ATOM 3089 OH2 TIP S 387 27.522 42.586 99.604 1.00 36.81 8 ATOM 3090 OH2 TIP S 388 53.393 35.796 132.475 1.00 45.12 8 ATOM 3091 OH2 TIP S 389 26.111 39.132 140.383 1.00 36.68 8 ATOM 3092 OH2 TIP S 390 41.149 33.935 91.197 1.00 44.11 8 ATOM 3093 OH2 TIP S 391 38.726 9.903 111.935 1.00 48.66 8 ATOM 3094 OH2 TIP S 392 44.037 20.151 107.791 1.00 47.15 8 ATOM 3095 OH2 TIP S 393 24.896 24.586 106.729 1.00 42.31 8 ATOM 3096 OH2 TIP S 394 48.692 42.557 136.545 1.00 47.73 8 ATOM 3097 OH2 TIP S 395 21.809 10.675 116.047 1.00 44.03 8 ATOM 3098 OH2 TIP S 396 42.924 51.849 99.818 1.00 45.40 8 ATOM 3099 OH2 TIP S 397 22.286 25.894 103.808 1.00 39.77 8 ATOM 3100 OH2 TIP S 398 43.206 44.710 140.038 1.00 46.92 8 ATOM 3101 OH2 TIP S 399 34.250 12.341 113.457 1.00 42.73 8 ATOM 3102 OH2 TIP S 400 38.615 29.176 148.856 1.00 40.99 8 ATOM 3103 OH2 TIP S 401 51.556 37.245 93.304 1.00 40.24 8 ATOM 3104 OH2 TIP S 402 36.303 22.463 141.392 1.00 39.99 8 ATOM 3105 OH2 TIP S 403 30.845 49.960 104.846 1.00 49.77 8 ATOM 3106 OH2 TIP S 404 47.708 48.566 134.215 1.00 48.93 8 ATOM 3107 OH2 TIP S 405 46.519 45.968 113.088 1.00 50.74 8 ATOM 3108 OH2 TIP S 406 30.362 6.706 116.525 1.00 46.93 8 ATOM 3109 OH2 TIP S 407 52.034 49.065 118.568 1.00 40.34 8 ATOM 3110 OH2 TIP S 408 36.643 17.245 109.715 1.00 49.93 8 ATOM 3111 OH2 TIP S 409 22.078 31.213 107.031 1.00 44.78 8 ATOM 3112 OH2 TIP S 410 58.653 41.437 102.107 1.00 40.48 8 ATOM 3113 OH2 TIP S 411 32.350 47.045 120.866 1.00 48.98 8 ATOM 3114 OH2 TIP S 412 59.398 33.349 102.328 1.00 47.56 8 ATOM 3115 OH2 TIP S 413 57.462 38.698 128.563 1.00 48.98 8 ATOM 3116 OH2 TIP S 414 34.294 20.012 141.097 1.00 37.72 8 ATOM 3117 OH2 TIP S 415 43.340 50.963 135.774 1.00 44.07 8 ATOM 3118 OH2 TIP S 416 29.810 36.408 142.540 1.00 41.10 8 ATOM 3119 OH2 TIP S 417 46.862 48.645 122.775 1.00 47.51 8 END ATOM 2796 OH2 TIP S 94 42.067 23.372 209.100 1.00 27.04 S ATOM 2797 OH2 TIP S 95 26.927 13.464 192.094 1.00 17.75 S ATOM 2798 OH2 TIP S 96 23.655 31.513 191.345 1.00 25.01 S ATOM 2799 OH2 TIP S 97 44.315 49.513 160.272 1.00 36.39 S ATOM 2800 OH2 TIP S 98 57.833 30.994 173.683 1.00 26.75 S ATOM 2801 OH2 TIP S 99 26.800 22.613 170.688 1.00 25.00 S ATOM 2802 OH2 TIP S 100 22.680 27.785 189.184 1.00 22.86 S ATOM 2803 OH2 TIP S 101 25.625 30.635 172.909 1.00 23.36 S ATOM 2804 OH2 TIP S 102 38.646 11.391 198.740 1.00 25.76 S ATOM 2805 OH2 TIP S 103 54.552 30.397 194.009 1.00 19.46 S ATOM 2806 OH2 TIP S 104 38.651 14.663 202.522 1.00 33.79 S ATOM 2807 OH2 TIP S 105 59.939 33.390 170.161 1.00 40.87 S ATOM 2808 OH2 TIP S 106 56.547 24.130 162.578 1.00 30.87 S ATOM 2809 OH2 TIP S 107 59.123 32.997 172.927 1.00 23.82 S ATOM 2810 OH2 TIP S 108 16.258 27.458 188.150 1.00 24.41 S ATOM 2811 OH2 TIP S 109 19.966 25.088 173.794 1.00 29.67 S ATOM 2812 OH2 TIP S 110 21.402 38.440 185.833 1.00 38.67 S ATOM 2813 OH2 TIP S 111 28.429 35.246 163.155 1.00 71.86 S ATOM 2814 OH2 TIP S 112 38.403 6.830 197.369 1.00 32.52 S ATOM 2815 OH2 TIP S 113 30.228 43.749 202.548 1.00 29.22 S ATOM 2816 OH2 TIP S 114 39.601 24.423 170.556 1.00 53.39 S ATOM 2817 OH2 TIP S 115 42.640 13.003 178.958 1.00 29.22 S ATOM 2818 OH2 TIP S 116 22.555 29.731 199.167 1.00 38.31 S ATOM 2819 OH2 TIP S 117 14.339 24.524 184.657 1.00 31.37 S ATOM 2820 OH2 TIP S 118 43.835 16.827 178.105 1.00 33.90 S ATOM 2821 OH2 TIP S 119 25.215 43.521 198.753 1.00 27.12 S ATOM 2822 OH2 TIP S 120 41.276 37.770 203.256 1.00 24.26 S ATOM 2823 OH2 TIP S 121 58.611 39.813 187.819 1.00 34.65 S ATOM 2824 OH2 TIP S 122 40.539 18.220 177.941 1.00 23.96 S ATOM 2825 OH2 TIP S 123 50.765 22.768 189.329 1.00 34.68 S ATOM 2826 OH2 TIP S 124 46.457 46.638 183.464 1.00 26.39 S ATOM 2827 OH2 TIP S 125 56.912 32.719 163.774 1.00 34.48 S ATOM 2828 OH2 TIP S 126 31.638 8.254 183.342 1.00 20.78 S ATOM 2829 OH2 TIP S 127 58.566 30.181 177.126 1.00 19.66 S ATOM 2830 OH2 TIP S 128 21.212 21.887 187.696 1.00 22.94 S ATOM 2831 OH2 TIP S 129 43.393 43.606 183.469 1.00 37.28 S ATOM 2832 OH2 TIP S 130 41.636 45.401 198.980 1.00 29.59 S ATOM 2833 OH2 TIP S 131 24.197 18.989 174.210 1.00 22.41 S ATOM 2834 OH2 TIP S 132 55.467 49.014 187.134 1.00 34.28 S ATOM 2835 OH2 TIP S 133 42.643 41.055 153.000 1.00 37.84 S ATOM 2836 OH2 TIP S 134 19.686 29.647 193.374 1.00 31.62 S ATOM 2837 OH2 TIP S 135 16.611 29.520 179.818 1.00 22.23 S ATOM 2838 OH2 TIP S 136 57.173 27.973 193.533 1.00 34.16 S ATOM 2839 OH2 TIP S 137 46.673 13.556 194.397 1.00 35.31 S ATOM 2840 OH2 TIP S 138 31.569 48.735 164.662 1.00 42.74 S ATOM 2841 OH2 TIP S 139 53.876 21.633 187.456 1.00 35.40 S ATOM 2842 OH2 TIP S 140 52.132 20.711 203.805 1.00 30.39 S ATOM 2843 OH2 TIP S 141 51.320 42.885 195.759 1.00 28.93 S ATOM 2844 OH2 TIP S 142 44.387 32.976 203.357 1.00 30.89 S ATOM 2845 OH2 TIP S 143 38.623 22.478 171.764 1.00 32.42 S ATOM 2846 OH2 TIP S 144 25.592 38.833 189.507 1.00 41.27 S ATOM 2847 OH2 TIP S 145 23.352 26.633 170.925 1.00 35.02 S ATOM 2848 OH2 TIP S 146 46.785 34.483 203.777 1.00 39.25 S ATOM 2849 OH2 TIP S 147 28.918 30.213 172.863 1.00 32.61 S ATOM 2850 OH2 TIP S 148 52.476 35.831 198.410 1.00 30.47 S ATOM 2851 OH2 TIP S 149 28.524 40.341 159.791 1.00 37.22 S ATOM 2852 OH2 TIP S 150 24.746 26.566 165.663 1.00 31.73 S ATOM 2853 OH2 TIP S 152 21.318 32.655 191.358 1.00 28.87 S

[0622] TABLE 7 Coordinate data for PKB S474D REMARK coordinates from restrained individual B-factor refinement REMARK refinement resolution: 500.0-1.6 A REMARK starting r = 0.2057 free_r = 0.2340 REMARK final r = 0.2049 free_r = 0.2345 REMARK B rmsd for bonded mainchain atoms = 1.267 target = 1.5 REMARK B rmsd for bonded sidechain atoms = 1.886 target = 2.0 REMARK B rmsd for angle mainchain atoms = 2.013 target = 2.0 REMARK B rmsd for angle sidechain atoms = 2.871 target = 2.5 REMARK rweight = 0.1000 (with wa = 1.01586) REMARK target = mlf steps = 30 REMARK sg = P2 (1) 2 (1) 2 (1) a = 44.906 b = 60.998 c = 129.410 alpha = 90 beta = 90 gamma = 90 REMARK parameter file 1: protein.param REMARK parameter file 2: anp.par REMARK parameter file 3: CNS_TOPPAR: ion.param REMARK parameter file 4: CNS_TOPPAR: water_rep.param REMARK molecular structure file: generate_easy.mtf REMARK input coordinates: minimize.pdb REMARK reflection file = pkb-s474d-free.hkl REMARK ncs = none REMARK B-correction resolution: 6.0-1.6 REMARK initial B-factor correction applied to fobs: REMARK B11 = 4.041 B22 = 3.016 B33 = −7.057 REMARK B12 = 0.000 B13 = 0.000 B23 = 0.000 REMARK B-factor correction applied to coordinate array B: −0.072 REMARK bulk solvent: density level = 0.337514 e/A{circumflex over ( )}3, B-factor = 17.3248 A{circumflex over ( )}2 REMARK reflections with |Fobs|/sigma_F < 0.0 rejected REMARK reflections with |Fobs| > 10000 * rms (Fobs) rejected REMARK theoretical total number of refl. in resol. range: 47803 (100.0%) REMARK number of unobserved reflections (no entry or |F|=0): 17202 (36.0%) REMARK number of reflections rejected: 0 (0.0%) REMARK total number of reflections used: 30601 (64.0%) REMARK number of reflections in working set: 29084 (60.8%) REMARK number of reflections in test set: 1517 (3.2%) CRYST1 44.906 60.998 129.410 90.00 90.00 90.00 P 21 21 21 REMARK FILENAME=“bindividual.pdb” REMARK DATE: 10-Jul-02 12:01:24 created by user: dbarford REMARK VERSION: 1.1 ATOM 1 CB LYS A 146 35.991 47.970 155.511 1.00 46.78 A ATOM 2 CG LYS A 146 35.552 46.519 155.327 1.00 48.24 A ATOM 3 CD LYS A 146 35.012 46.271 153.930 1.00 49.40 A ATOM 4 CE LYS A 146 34.523 44.840 153.779 1.00 49.88 A ATOM 5 NZ LYS A 146 33.881 44.612 152.453 1.00 50.89 A ATOM 6 C LYS A 146 37.792 47.796 157.271 1.00 44.89 A ATOM 7 O LYS A 146 38.804 48.458 157.011 1.00 45.12 A ATOM 8 N LYS A 146 36.358 49.816 157.132 1.00 45.98 A ATOM 9 CA LYS A 146 36.396 48.335 156.947 1.00 45.62 A ATOM 10 N VAL A 147 37.827 46.598 157.859 1.00 42.77 A ATOM 11 CA VAL A 147 39.074 45.936 158.259 1.00 40.74 A ATOM 12 CB VAL A 147 39.056 45.539 159.772 1.00 40.55 A ATOM 13 CG1 VAL A 147 40.474 45.391 160.300 1.00 39.85 A ATOM 14 CG2 VAL A 147 38.283 46.556 160.605 1.00 40.90 A ATOM 15 C VAL A 147 39.307 44.670 157.424 1.00 38.88 A ATOM 16 O VAL A 147 38.397 43.851 157.259 1.00 38.52 A ATOM 17 N THR A 148 40.528 44.525 156.904 1.00 37.71 A ATOM 18 CA THR A 148 40.915 43.370 156.084 1.00 37.31 A ATOM 19 CB THR A 148 41.229 43.776 154.611 1.00 37.93 A ATOM 20 OG1 THR A 148 42.165 44.860 154.591 1.00 39.40 A ATOM 21 CG2 THR A 148 39.959 44.175 153.862 1.00 37.85 A ATOM 22 C THR A 148 42.116 42.611 156.662 1.00 35.95 A ATOM 23 O THR A 148 42.756 43.070 157.613 1.00 35.13 A ATOM 24 N MET A 149 42.417 41.459 156.061 1.00 35.36 A ATOM 25 CA MET A 149 43.520 40.577 156.462 1.00 34.92 A ATOM 26 CB MET A 149 43.414 39.255 155.691 1.00 36.33 A ATOM 27 CG MET A 149 43.998 38.040 156.391 1.00 38.13 A ATOM 28 SD MET A 149 43.030 37.531 157.828 1.00 40.90 A ATOM 29 CE MET A 149 42.120 36.200 157.139 1.00 38.85 A ATOM 30 C MET A 149 44.907 41.197 156.230 1.00 33.99 A ATOM 31 O MET A 149 45.818 41.014 157.043 1.00 32.97 A ATOM 32 N ASN A 150 45.032 41.964 155.146 1.00 33.65 A ATOM 33 CA ASN A 150 46.287 42.620 154.761 1.00 33.79 A ATOM 34 CB ASN A 150 46.310 42.887 153.242 1.00 37.25 A ATOM 35 CG ASN A 150 45.099 43.676 152.756 1.00 39.85 A ATOM 36 OD1 ASN A 150 44.990 44.882 152.990 1.00 42.32 A ATOM 37 ND2 ASN A 150 44.191 42.996 152.066 1.00 41.41 A ATOM 38 C ASN A 150 46.680 43.885 155.543 1.00 31.77 A ATOM 39 O ASN A 150 47.716 44.494 155.261 1.00 32.40 A ATOM 40 N ASP A 151 45.857 44.272 156.518 1.00 29.24 A ATOM 41 CA ASP A 151 46.121 45.449 157.357 1.00 27.13 A ATOM 42 CB ASP A 151 44.805 46.053 157.876 1.00 28.08 A ATOM 43 CG ASP A 151 43.957 46.667 156.775 1.00 30.02 A ATOM 44 OD1 ASP A 151 44.517 47.317 155.864 1.00 31.91 A ATOM 45 OD2 ASP A 151 42.720 46.509 156.833 1.00 30.02 A ATOM 46 C ASP A 151 47.005 45.083 158.551 1.00 25.59 A ATOM 47 O ASP A 151 47.368 45.944 159.361 1.00 24.48 A ATOM 48 N PHE A 152 47.331 43.793 158.652 1.00 24.32 A ATOM 49 CA PHE A 152 48.139 43.255 159.745 1.00 23.75 A ATOM 50 CB PHE A 152 47.290 42.314 160.624 1.00 22.47 A ATOM 51 CG PHE A 152 46.049 42.951 161.191 1.00 22.06 A ATOM 52 CD1 PHE A 152 46.090 43.627 162.424 1.00 22.19 A ATOM 53 CD2 PHE A 152 44.835 42.908 160.477 1.00 21.35 A ATOM 54 CE1 PHE A 152 44.932 44.265 162.947 1.00 21.99 A ATOM 55 CE2 PHE A 152 43.670 43.537 160.981 1.00 20.95 A ATOM 56 CZ PHE A 152 43.719 44.219 162.220 1.00 21.29 A ATOM 57 C PHE A 152 49.380 42.492 159.296 1.00 23.26 A ATOM 58 O PHE A 152 49.446 41.981 158.173 1.00 23.87 A ATOM 59 N GLU A 153 50.355 42.430 160.202 1.00 23.42 A ATOM 60 CA GLU A 153 51.610 41.700 160.015 1.00 23.74 A ATOM 61 CB GLU A 153 52.808 42.571 160.394 1.00 26.53 A ATOM 62 CG GLU A 153 53.159 43.619 159.359 1.00 31.28 A ATOM 63 CD GLU A 153 54.006 44.732 159.923 1.00 34.15 A ATOM 64 OE1 GLU A 153 55.220 44.768 159.627 1.00 38.38 A ATOM 65 OE2 GLU A 153 53.458 45.575 160.666 1.00 36.09 A ATOM 66 C GLU A 153 51.506 40.512 160.966 1.00 23.22 A ATOM 67 O GLU A 153 51.255 40.695 162.155 1.00 22.59 A ATOM 68 N TYR A 154 51.656 39.304 160.427 1.00 22.72 A ATOM 69 CA TYR A 154 51.552 38.063 161.200 1.00 22.21 A ATOM 70 CB TYR A 154 50.833 36.991 160.362 1.00 22.82 A ATOM 71 CG TYR A 154 49.442 37.436 159.938 1.00 21.25 A ATOM 72 CD1 TYR A 154 49.261 38.289 158.821 1.00 21.61 A ATOM 73 CE1 TYR A 154 47.985 38.830 158.502 1.00 22.05 A ATOM 74 CD2 TYR A 154 48.310 37.115 160.717 1.00 21.58 A ATOM 75 CE2 TYR A 154 47.024 37.650 160.407 1.00 22.01 A ATOM 76 CZ TYR A 154 46.878 38.511 159.304 1.00 21.58 A ATOM 77 OH TYR A 154 45.660 39.090 159.037 1.00 20.58 A ATOM 78 C TYR A 154 52.928 37.617 161.686 1.00 22.76 A ATOM 79 O TYR A 154 53.755 37.127 160.913 1.00 22.34 A ATOM 80 N LEU A 155 53.156 37.815 162.984 1.00 22.84 A ATOM 81 CA LEU A 155 54.436 37.517 163.631 1.00 23.49 A ATOM 82 CB LEU A 155 54.709 38.548 164.732 1.00 22.23 A ATOM 83 CG LEU A 155 54.516 40.018 164.322 1.00 23.82 A ATOM 84 CD1 LEU A 155 54.699 40.891 165.524 1.00 25.47 A ATOM 85 CD2 LEU A 155 55.470 40.434 163.196 1.00 24.24 A ATOM 86 C LEU A 155 54.654 36.095 164.140 1.00 23.77 A ATOM 87 O LEU A 155 55.531 35.394 163.627 1.00 25.45 A ATOM 88 N LYS A 156 53.899 35.681 165.161 1.00 23.72 A ATOM 89 CA LYS A 156 54.022 34.324 165.713 1.00 23.83 A ATOM 90 CB LYS A 156 55.243 34.177 166.642 1.00 26.51 A ATOM 91 CG LYS A 156 55.446 35.236 167.710 1.00 28.39 A ATOM 92 CD LYS A 156 56.739 34.935 168.446 1.00 30.20 A ATOM 93 CE LYS A 156 57.547 36.187 168.697 1.00 31.27 A ATOM 94 NZ LYS A 156 58.763 35.906 169.507 1.00 30.91 A ATOM 95 C LYS A 156 52.778 33.759 166.381 1.00 22.12 A ATOM 96 O LYS A 156 51.905 34.503 166.832 1.00 20.31 A ATOM 97 N LEU A 157 52.713 32.427 166.427 1.00 20.31 A ATOM 98 CA LEU A 157 51.596 31.698 167.025 1.00 17.99 A ATOM 99 CB LEU A 157 51.590 30.244 166.529 1.00 18.27 A ATOM 100 CG LEU A 157 50.460 29.295 166.950 1.00 17.24 A ATOM 101 CD1 LEU A 157 49.163 29.686 166.272 1.00 18.35 A ATOM 102 CD2 LEU A 157 50.828 27.874 166.586 1.00 17.81 A ATOM 103 C LEU A 157 51.663 31.740 168.551 1.00 17.21 A ATOM 104 O LEU A 157 52.695 31.428 169.147 1.00 16.26 A ATOM 105 N LEU A 158 50.559 32.157 169.164 1.00 16.20 A ATOM 106 CA LEU A 158 50.453 32.247 170.620 1.00 15.54 A ATOM 107 CB LEU A 158 49.637 33.476 171.017 1.00 14.60 A ATOM 108 CG LEU A 158 50.188 34.849 170.645 1.00 14.10 A ATOM 109 CD1 LEU A 158 49.148 35.897 170.959 1.00 14.40 A ATOM 110 CD2 LEU A 158 51.503 35.133 171.371 1.00 13.46 A ATOM 111 C LEU A 158 49.793 31.007 171.200 1.00 15.73 A ATOM 112 O LEU A 158 50.201 30.514 172.253 1.00 15.26 A ATOM 113 N GLY A 159 48.777 30.512 170.497 1.00 16.92 A ATOM 114 CA GLY A 159 48.054 29.339 170.948 1.00 19.04 A ATOM 115 C GLY A 159 47.246 28.690 169.848 1.00 22.76 A ATOM 116 O GLY A 159 46.961 29.312 168.821 1.00 20.44 A ATOM 117 N LYS A 160 46.856 27.441 170.084 1.00 26.41 A ATOM 118 CA LYS A 160 46.080 26.670 169.120 1.00 31.69 A ATOM 119 CB LYS A 160 47.021 25.810 168.263 1.00 33.56 A ATOM 120 CG LYS A 160 46.474 25.406 166.902 1.00 37.49 A ATOM 121 CD LYS A 160 47.561 24.765 166.051 1.00 39.02 A ATOM 122 CE LYS A 160 47.085 24.532 164.623 1.00 40.97 A ATOM 123 NZ LYS A 160 48.162 23.969 163.761 1.00 42.36 A ATOM 124 C LYS A 160 45.072 25.784 169.841 1.00 34.91 A ATOM 125 O LYS A 160 45.374 25.197 170.885 1.00 35.09 A ATOM 126 N GLY A 161 43.865 25.733 169.287 1.00 37.41 A ATOM 127 CA GLY A 161 42.804 24.908 169.835 1.00 40.92 A ATOM 128 C GLY A 161 42.480 23.808 168.842 1.00 42.89 A ATOM 129 O GLY A 161 43.197 23.628 167.849 1.00 43.97 A ATOM 130 N THR A 162 41.399 23.077 169.101 1.00 44.70 A ATOM 131 CA THR A 162 40.957 21.988 168.226 1.00 45.93 A ATOM 132 CB THR A 162 40.212 20.882 169.044 1.00 46.60 A ATOM 133 OG1 THR A 162 40.875 20.686 170.301 1.00 46.54 A ATOM 134 CG2 THR A 162 40.223 19.546 168.298 1.00 46.54 A ATOM 135 C THR A 162 40.044 22.560 167.123 1.00 46.32 A ATOM 136 O THR A 162 39.621 21.839 166.215 1.00 47.55 A ATOM 137 N PHE A 163 39.763 23.864 167.210 1.00 46.08 A ATOM 138 CA PHE A 163 38.908 24.567 166.249 1.00 45.94 A ATOM 139 CB PHE A 163 37.654 25.139 166.941 1.00 48.60 A ATOM 140 CG PHE A 163 36.868 24.129 167.749 1.00 50.85 A ATOM 141 CD1 PHE A 163 36.739 24.285 169.144 1.00 51.89 A ATOM 142 CD2 PHE A 163 36.253 23.019 167.128 1.00 52.06 A ATOM 143 CE1 PHE A 163 36.006 23.345 169.928 1.00 53.11 A ATOM 144 CE2 PHE A 163 35.515 22.065 167.892 1.00 52.93 A ATOM 145 CZ PHE A 163 35.391 22.230 169.297 1.00 53.36 A ATOM 146 C PHE A 163 39.639 25.704 165.522 1.00 44.28 A ATOM 147 O PHE A 163 39.503 25.844 164.300 1.00 44.95 A ATOM 148 N GLY A 164 40.402 26.506 166.272 1.00 41.78 A ATOM 149 CA GLY A 164 41.128 27.628 165.686 1.00 37.51 A ATOM 150 C GLY A 164 42.459 28.002 166.319 1.00 34.67 A ATOM 151 O GLY A 164 42.857 27.432 167.340 1.00 34.02 A ATOM 152 N LYS A 165 43.128 28.989 165.718 1.00 30.49 A ATOM 153 CA LYS A 165 44.437 29.464 166.175 1.00 26.36 A ATOM 154 CB LYS A 165 45.507 29.144 165.119 1.00 28.07 A ATOM 155 CG LYS A 165 45.213 29.664 163.712 1.00 29.66 A ATOM 156 CD LYS A 165 46.250 29.187 162.712 1.00 31.90 A ATOM 157 CE LYS A 165 45.887 29.629 161.304 1.00 34.12 A ATOM 158 NZ LYS A 165 46.866 29.140 160.292 1.00 36.61 A ATOM 159 C LYS A 165 44.494 30.949 166.553 1.00 23.30 A ATOM 160 O LYS A 165 43.719 31.758 166.041 1.00 22.11 A ATOM 161 N VAL A 166 45.405 31.285 167.473 1.00 18.51 A ATOM 162 CA VAL A 166 45.605 32.664 167.946 1.00 16.12 A ATOM 163 CB VAL A 166 45.335 32.813 169.478 1.00 14.80 A ATOM 164 CG1 VAL A 166 45.444 34.284 169.914 1.00 13.52 A ATOM 165 CG2 VAL A 166 43.945 32.289 169.823 1.00 14.78 A ATOM 166 C VAL A 166 47.033 33.096 167.602 1.00 14.71 A ATOM 167 O VAL A 166 48.002 32.486 168.051 1.00 13.66 A ATOM 168 N ILE A 167 47.135 34.146 166.789 1.00 14.33 A ATOM 169 CA ILE A 167 48.413 34.683 166.311 1.00 13.86 A ATOM 170 CB ILE A 167 48.456 34.630 164.725 1.00 15.99 A ATOM 171 CG2 ILE A 167 49.737 35.282 164.164 1.00 15.76 A ATOM 172 CG1 ILE A 167 48.376 33.172 164.237 1.00 17.11 A ATOM 173 CD1 ILE A 167 48.112 33.004 162.746 1.00 19.50 A ATOM 174 C ILE A 167 48.660 36.123 166.789 1.00 12.81 A ATOM 175 O ILE A 167 47.738 36.939 166.818 1.00 13.42 A ATOM 176 N LEU A 168 49.912 36.421 167.153 1.00 13.57 A ATOM 177 CA LEU A 168 50.321 37.769 167.568 1.00 13.34 A ATOM 178 CB LEU A 168 51.657 37.741 168.331 1.00 13.85 A ATOM 179 CG LEU A 168 52.360 39.064 168.686 1.00 14.31 A ATOM 180 CD1 LEU A 168 51.474 39.963 169.534 1.00 15.36 A ATOM 181 CD2 LEU A 168 53.660 38.775 169.396 1.00 15.22 A ATOM 182 C LEU A 168 50.480 38.586 166.288 1.00 13.78 A ATOM 183 O LEU A 168 51.263 38.219 165.405 1.00 13.96 A ATOM 184 N VAL A 169 49.693 39.656 166.188 1.00 13.83 A ATOM 185 CA VAL A 169 49.705 40.532 165.020 1.00 16.50 A ATOM 186 CB VAL A 169 48.338 40.496 164.242 1.00 15.39 A ATOM 187 CG1 VAL A 169 48.027 39.095 163.770 1.00 16.18 A ATOM 188 CG2 VAL A 169 47.183 41.021 165.095 1.00 15.89 A ATOM 189 C VAL A 169 50.062 41.980 165.348 1.00 17.03 A ATOM 190 O VAL A 169 49.970 42.410 166.497 1.00 16.28 A ATOM 191 N ARG A 170 50.493 42.710 164.323 1.00 18.98 A ATOM 192 CA ARG A 170 50.835 44.120 164.449 1.00 20.17 A ATOM 193 CB ARG A 170 52.344 44.340 164.249 1.00 21.99 A ATOM 194 CG ARG A 170 52.798 45.811 164.246 1.00 24.54 A ATOM 195 CD ARG A 170 54.319 45.972 164.189 1.00 26.69 A ATOM 196 NE ARG A 170 54.944 45.240 163.086 1.00 30.34 A ATOM 197 CZ ARG A 170 56.024 44.466 163.202 1.00 31.30 A ATOM 198 NH1 ARG A 170 56.622 44.305 164.377 1.00 31.59 A ATOM 199 NH2 ARG A 170 56.503 43.840 162.134 1.00 33.00 A ATOM 200 C ARG A 170 50.032 44.846 163.379 1.00 20.88 A ATOM 201 O ARG A 170 50.069 44.463 162.207 1.00 21.21 A ATOM 202 N GLU A 171 49.264 45.851 163.800 1.00 20.64 A ATOM 203 CA GLU A 171 48.459 46.658 162.884 1.00 22.06 A ATOM 204 CB GLU A 171 47.360 47.405 163.650 1.00 22.82 A ATOM 205 CG GLU A 171 46.315 48.084 162.753 1.00 24.90 A ATOM 206 CD GLU A 171 45.188 48.772 163.516 1.00 26.38 A ATOM 207 OE1 GLU A 171 45.287 48.974 164.748 1.00 28.56 A ATOM 208 OE2 GLU A 171 44.186 49.126 162.864 1.00 29.84 A ATOM 209 C GLU A 171 49.417 47.632 162.196 1.00 22.37 A ATOM 210 O GLU A 171 50.087 48.419 162.864 1.00 22.45 A ATOM 211 N LYS A 172 49.508 47.525 160.871 1.00 23.08 A ATOM 212 CA LYS A 172 50.400 48.350 160.045 1.00 25.36 A ATOM 213 CB LYS A 172 50.238 47.985 158.567 1.00 24.67 A ATOM 214 CG LYS A 172 50.701 46.585 158.206 1.00 25.16 A ATOM 215 CD LYS A 172 50.441 46.283 156.741 1.00 26.03 A ATOM 216 CE LYS A 172 50.894 44.882 156.373 1.00 27.30 A ATOM 217 NZ LYS A 172 50.627 44.564 154.941 1.00 28.64 A ATOM 218 C LYS A 172 50.278 49.865 160.206 1.00 25.97 A ATOM 219 O LYS A 172 51.289 50.555 160.371 1.00 27.02 A ATOM 220 N ALA A 173 49.039 50.358 160.221 1.00 27.17 A ATOM 221 CA ALA A 173 48.744 51.788 160.340 1.00 27.54 A ATOM 222 CB ALA A 173 47.296 52.054 159.941 1.00 28.28 A ATOM 223 C ALA A 173 49.044 52.437 161.689 1.00 28.27 A ATOM 224 O ALA A 173 49.482 53.589 161.734 1.00 29.02 A ATOM 225 N THR A 174 48.838 51.687 162.774 1.00 28.12 A ATOM 226 CA THR A 174 49.053 52.193 164.133 1.00 26.80 A ATOM 227 CB THR A 174 47.841 51.887 165.045 1.00 27.59 A ATOM 228 OG1 THR A 174 47.652 50.469 165.132 1.00 25.96 A ATOM 229 CG2 THR A 174 46.568 52.542 164.511 1.00 25.92 A ATOM 230 C THR A 174 50.319 51.694 164.839 1.00 27.09 A ATOM 231 O THR A 174 50.823 52.356 165.755 1.00 26.75 A ATOM 232 N GLY A 175 50.816 50.528 164.425 1.00 26.61 A ATOM 233 CA GLY A 175 52.006 49.947 165.034 1.00 27.34 A ATOM 234 C GLY A 175 51.710 49.208 166.331 1.00 27.13 A ATOM 235 O GLY A 175 52.626 48.705 166.987 1.00 27.15 A ATOM 236 N ARG A 176 50.426 49.146 166.690 1.00 26.58 A ATOM 237 CA ARG A 176 49.963 48.480 167.909 1.00 25.46 A ATOM 238 CB ARG A 176 48.637 49.082 168.377 1.00 28.67 A ATOM 239 CG ARG A 176 48.748 50.519 168.855 1.00 32.16 A ATOM 240 CD ARG A 176 47.390 51.087 169.205 1.00 35.83 A ATOM 241 NE ARG A 176 47.473 52.504 169.554 1.00 40.39 A ATOM 242 CZ ARG A 176 46.468 53.372 169.450 1.00 42.09 A ATOM 243 NH1 ARG A 176 45.279 52.984 169.001 1.00 43.47 A ATOM 244 NH2 ARG A 176 46.654 54.638 169.796 1.00 43.14 A ATOM 245 C ARG A 176 49.828 46.973 167.728 1.00 24.01 A ATOM 246 O ARG A 176 49.442 46.495 166.656 1.00 23.61 A ATOM 247 N TYR A 177 50.155 46.237 168.790 1.00 21.65 A ATOM 248 CA TYR A 177 50.114 44.779 168.787 1.00 20.54 A ATOM 249 CB TYR A 177 51.336 44.212 169.514 1.00 20.61 A ATOM 250 CG TYR A 177 52.662 44.516 168.843 1.00 22.82 A ATOM 251 CD1 TYR A 177 53.195 45.828 168.833 1.00 24.24 A ATOM 252 CE1 TYR A 177 54.457 46.110 168.237 1.00 25.32 A ATOM 253 CD2 TYR A 177 53.415 43.490 168.241 1.00 23.65 A ATOM 254 CE2 TYR A 177 54.679 43.761 167.644 1.00 26.72 A ATOM 255 CZ TYR A 177 55.187 45.069 167.648 1.00 26.11 A ATOM 256 OH TYR A 177 56.406 45.327 167.061 1.00 28.14 A ATOM 257 C TYR A 177 48.833 44.211 169.377 1.00 19.07 A ATOM 258 O TYR A 177 48.320 44.715 170.379 1.00 19.67 A ATOM 259 N TYR A 178 48.297 43.189 168.709 1.00 17.60 A ATOM 260 CA TYR A 178 47.057 42.529 169.116 1.00 17.11 A ATOM 261 CB TYR A 178 45.877 43.019 168.261 1.00 17.47 A ATOM 262 CG TYR A 178 45.579 44.507 168.316 1.00 19.26 A ATOM 263 CD1 TYR A 178 45.920 45.349 167.234 1.00 19.57 A ATOM 264 CE1 TYR A 178 45.670 46.749 167.283 1.00 21.58 A ATOM 265 CD2 TYR A 178 44.977 45.089 169.452 1.00 19.12 A ATOM 266 CE2 TYR A 178 44.723 46.489 169.516 1.00 22.32 A ATOM 267 CZ TYR A 178 45.075 47.307 168.427 1.00 22.02 A ATOM 268 OH TYR A 178 44.845 48.660 168.483 1.00 26.18 A ATOM 269 C TYR A 178 47.155 41.012 168.964 1.00 15.27 A ATOM 270 O TYR A 178 48.116 40.493 168.396 1.00 15.12 A ATOM 271 N ALA A 179 46.167 40.307 169.510 1.00 13.73 A ATOM 272 CA ALA A 179 46.093 38.856 169.401 1.00 12.88 A ATOM 273 CB ALA A 179 45.920 38.224 170.770 1.00 13.44 A ATOM 274 C ALA A 179 44.891 38.556 168.513 1.00 12.57 A ATOM 275 O ALA A 179 43.766 38.952 168.830 1.00 11.35 A ATOM 276 N MET A 180 45.141 37.912 167.376 1.00 12.14 A ATOM 277 CA MET A 180 44.070 37.577 166.444 1.00 12.46 A ATOM 278 CB MET A 180 44.448 37.959 165.006 1.00 13.41 A ATOM 279 CG MET A 180 43.265 37.956 164.032 1.00 16.23 A ATOM 280 SD MET A 180 43.740 38.002 162.294 1.00 18.09 A ATOM 281 CE MET A 180 44.079 39.712 162.118 1.00 18.60 A ATOM 282 C MET A 180 43.656 36.113 166.488 1.00 12.76 A ATOM 283 O MET A 180 44.453 35.229 166.180 1.00 11.58 A ATOM 284 N LYS A 181 42.404 35.870 166.877 1.00 12.35 A ATOM 285 CA LYS A 181 41.858 34.520 166.909 1.00 13.81 A ATOM 286 CB LYS A 181 40.824 34.352 168.031 1.00 13.00 A ATOM 287 CG LYS A 181 40.321 32.921 168.189 1.00 14.36 A ATOM 288 CD LYS A 181 39.412 32.758 169.383 1.00 12.64 A ATOM 289 CE LYS A 181 38.950 31.313 169.497 1.00 14.72 A ATOM 290 NZ LYS A 181 38.167 31.096 170.745 1.00 13.62 A ATOM 291 C LYS A 181 41.219 34.277 165.541 1.00 15.58 A ATOM 292 O LYS A 181 40.275 34.975 165.150 1.00 15.91 A ATOM 293 N ILE A 182 41.793 33.329 164.804 1.00 16.92 A ATOM 294 CA ILE A 182 41.332 32.963 163.467 1.00 18.77 A ATOM 295 CB ILE A 182 42.521 32.887 162.455 1.00 18.33 A ATOM 296 CG2 ILE A 182 42.015 32.506 161.055 1.00 19.77 A ATOM 297 CG1 ILE A 182 43.251 34.237 162.391 1.00 18.27 A ATOM 298 CD1 ILE A 182 44.575 34.219 161.643 1.00 19.42 A ATOM 299 C ILE A 182 40.587 31.627 163.502 1.00 19.51 A ATOM 300 O ILE A 182 41.125 30.611 163.955 1.00 20.62 A ATOM 301 N LEU A 183 39.341 31.656 163.035 1.00 19.80 A ATOM 302 CA LEU A 183 38.482 30.475 162.980 1.00 20.88 A ATOM 303 CB LEU A 183 37.231 30.684 163.846 1.00 22.23 A ATOM 304 CG LEU A 183 37.343 30.798 165.375 1.00 22.62 A ATOM 305 CD1 LEU A 183 36.011 31.217 165.953 1.00 25.26 A ATOM 306 CD2 LEU A 183 37.779 29.481 165.990 1.00 24.84 A ATOM 307 C LEU A 183 38.079 30.193 161.530 1.00 20.98 A ATOM 308 O LEU A 183 37.784 31.116 160.770 1.00 20.81 A ATOM 309 N ARG A 184 38.100 28.917 161.151 1.00 22.37 A ATOM 310 CA ARG A 184 37.745 28.490 159.795 1.00 24.46 A ATOM 311 CB ARG A 184 38.528 27.230 159.413 1.00 26.64 A ATOM 312 CG ARG A 184 40.037 27.412 159.350 1.00 31.44 A ATOM 313 CD ARG A 184 40.737 26.100 159.025 1.00 34.87 A ATOM 314 NE ARG A 184 42.175 26.286 158.834 1.00 39.41 A ATOM 315 CZ ARG A 184 42.825 26.078 157.689 1.00 40.55 A ATOM 316 NH1 ARG A 184 42.177 25.665 156.604 1.00 40.86 A ATOM 317 NH2 ARG A 184 44.131 26.306 157.623 1.00 41.12 A ATOM 318 C ARG A 184 36.242 28.236 159.673 1.00 23.47 A ATOM 319 O ARG A 184 35.684 27.423 160.418 1.00 23.44 A ATOM 320 N LYS A 185 35.605 28.926 158.723 1.00 23.71 A ATOM 321 CA LYS A 185 34.159 28.824 158.472 1.00 25.34 A ATOM 322 CB LYS A 185 33.729 29.765 157.342 1.00 25.67 A ATOM 323 CG LYS A 185 33.756 31.234 157.681 1.00 26.84 A ATOM 324 CD LYS A 185 33.158 32.059 156.551 1.00 27.13 A ATOM 325 CE LYS A 185 33.152 33.535 156.886 1.00 27.10 A ATOM 326 NZ LYS A 185 32.548 34.353 155.795 1.00 27.64 A ATOM 327 C LYS A 185 33.636 27.428 158.151 1.00 25.95 A ATOM 328 O LYS A 185 32.611 27.017 158.694 1.00 26.63 A ATOM 329 N GLU A 186 34.369 26.695 157.310 1.00 27.17 A ATOM 330 CA GLU A 186 33.989 25.345 156.878 1.00 28.65 A ATOM 331 CB GLU A 186 34.952 24.856 155.789 1.00 32.27 A ATOM 332 CG GLU A 186 34.361 23.808 154.845 1.00 38.31 A ATOM 333 CD GLU A 186 35.222 23.568 153.617 1.00 41.05 A ATOM 334 OE1 GLU A 186 35.835 22.481 153.523 1.00 43.72 A ATOM 335 OE2 GLU A 186 35.279 24.463 152.743 1.00 42.30 A ATOM 336 C GLU A 186 33.876 24.317 158.011 1.00 27.71 A ATOM 337 O GLU A 186 32.985 23.466 157.990 1.00 27.55 A ATOM 338 N VAL A 187 34.733 24.456 159.024 1.00 26.87 A ATOM 339 CA VAL A 187 34.760 23.567 160.196 1.00 26.83 A ATOM 340 CB VAL A 187 36.095 23.724 160.993 1.00 26.78 A ATOM 341 CG1 VAL A 187 36.257 22.610 162.027 1.00 27.09 A ATOM 342 CG2 VAL A 187 37.271 23.717 160.050 1.00 27.39 A ATOM 343 C VAL A 187 33.585 23.870 161.133 1.00 25.64 A ATOM 344 O VAL A 187 32.925 22.956 161.631 1.00 26.32 A ATOM 345 N ILE A 188 33.320 25.163 161.325 1.00 25.47 A ATOM 346 CA ILE A 188 32.245 25.663 162.186 1.00 25.33 A ATOM 347 CB ILE A 188 32.421 27.197 162.416 1.00 25.89 A ATOM 348 CG2 ILE A 188 31.205 27.820 163.117 1.00 25.29 A ATOM 349 CG1 ILE A 188 33.682 27.431 163.254 1.00 26.99 A ATOM 350 CD1 ILE A 188 34.062 28.868 163.415 1.00 28.36 A ATOM 351 C ILE A 188 30.843 25.308 161.668 1.00 25.57 A ATOM 352 O ILE A 188 29.974 24.911 162.452 1.00 24.31 A ATOM 353 N ILE A 189 30.649 25.418 160.353 1.00 25.77 A ATOM 354 CA ILE A 189 29.370 25.099 159.708 1.00 26.71 A ATOM 355 CB ILE A 189 29.313 25.675 158.244 1.00 27.02 A ATOM 356 CG2 ILE A 189 28.009 25.260 157.526 1.00 26.65 A ATOM 357 CG1 ILE A 189 29.386 27.209 158.291 1.00 25.94 A ATOM 358 CD1 ILE A 189 29.688 27.880 156.957 1.00 27.91 A ATOM 359 C ILE A 189 29.115 23.580 159.730 1.00 27.66 A ATOM 360 O ILE A 189 27.996 23.146 160.016 1.00 28.08 A ATOM 361 N ALA A 190 30.175 22.795 159.510 1.00 28.63 A ATOM 362 CA ALA A 190 30.106 21.328 159.494 1.00 29.95 A ATOM 363 CB ALA A 190 31.395 20.745 158.928 1.00 30.58 A ATOM 364 C ALA A 190 29.807 20.713 160.863 1.00 30.97 A ATOM 365 O ALA A 190 29.134 19.683 160.953 1.00 31.74 A ATOM 366 N LYS A 191 30.296 21.363 161.920 1.00 31.94 A ATOM 367 CA LYS A 191 30.088 20.907 163.295 1.00 32.19 A ATOM 368 CB LYS A 191 31.335 21.188 164.143 1.00 34.20 A ATOM 369 CG LYS A 191 32.515 20.271 163.839 1.00 37.34 A ATOM 370 CD LYS A 191 33.738 20.646 164.663 1.00 40.00 A ATOM 371 CE LYS A 191 34.896 19.688 164.411 1.00 41.29 A ATOM 372 NZ LYS A 191 36.125 20.078 165.167 1.00 42.38 A ATOM 373 C LYS A 191 28.845 21.523 163.948 1.00 31.73 A ATOM 374 O LYS A 191 28.551 21.239 165.115 1.00 31.84 A ATOM 375 N ASP A 192 28.116 22.341 163.173 1.00 30.78 A ATOM 376 CA ASP A 192 26.884 23.046 163.584 1.00 30.80 A ATOM 377 CB ASP A 192 25.731 22.038 163.812 1.00 33.11 A ATOM 378 CG ASP A 192 24.352 22.670 163.677 1.00 36.31 A ATOM 379 OD1 ASP A 192 23.725 22.955 164.719 1.00 39.17 A ATOM 380 OD2 ASP A 192 23.893 22.874 162.531 1.00 38.75 A ATOM 381 C ASP A 192 27.126 23.952 164.811 1.00 29.85 A ATOM 382 O ASP A 192 26.313 24.018 165.745 1.00 30.07 A ATOM 383 N GLU A 193 28.267 24.643 164.781 1.00 27.44 A ATOM 384 CA GLU A 193 28.694 25.538 165.858 1.00 25.61 A ATOM 385 CB GLU A 193 30.135 25.197 166.272 1.00 26.55 A ATOM 386 CG GLU A 193 30.288 23.902 167.071 1.00 27.57 A ATOM 387 CD GLU A 193 29.638 23.968 168.446 1.00 29.06 A ATOM 388 OE1 GLU A 193 30.037 24.835 169.254 1.00 29.31 A ATOM 389 OE2 GLU A 193 28.728 23.152 168.713 1.00 29.35 A ATOM 390 C GLU A 193 28.577 27.032 165.541 1.00 24.30 A ATOM 391 O GLU A 193 29.275 27.858 166.141 1.00 23.23 A ATOM 392 N VAL A 194 27.667 27.376 164.627 1.00 22.03 A ATOM 393 CA VAL A 194 27.438 28.764 164.204 1.00 21.39 A ATOM 394 CB VAL A 194 26.471 28.827 162.972 1.00 21.56 A ATOM 395 CG1 VAL A 194 26.205 30.276 162.532 1.00 22.36 A ATOM 396 CG2 VAL A 194 27.062 28.043 161.806 1.00 20.88 A ATOM 397 C VAL A 194 26.924 29.656 165.343 1.00 19.90 A ATOM 398 O VAL A 194 27.477 30.731 165.573 1.00 18.23 A ATOM 399 N ALA A 195 25.932 29.160 166.087 1.00 20.46 A ATOM 400 CA ALA A 195 25.311 29.881 167.206 1.00 19.76 A ATOM 401 CB ALA A 195 24.161 29.060 167.784 1.00 22.18 A ATOM 402 C ALA A 195 26.297 30.270 168.311 1.00 19.00 A ATOM 403 O ALA A 195 26.265 31.397 168.804 1.00 18.06 A ATOM 404 N HIS A 196 27.208 29.352 168.635 1.00 18.31 A ATOM 405 CA HIS A 196 28.232 29.574 169.655 1.00 17.97 A ATOM 406 CB HIS A 196 28.915 28.251 170.029 1.00 19.85 A ATOM 407 CG HIS A 196 28.093 27.368 170.920 1.00 21.21 A ATOM 408 CD2 HIS A 196 27.071 27.647 171.765 1.00 22.11 A ATOM 409 ND1 HIS A 196 28.305 26.010 171.015 1.00 23.75 A ATOM 410 CE1 HIS A 196 27.450 25.490 171.878 1.00 23.78 A ATOM 411 NE2 HIS A 196 26.690 26.463 172.347 1.00 22.56 A ATOM 412 C HIS A 196 29.279 30.608 169.226 1.00 16.92 A ATOM 413 O HIS A 196 29.736 31.409 170.046 1.00 16.75 A ATOM 414 N THR A 197 29.601 30.614 167.932 1.00 16.78 A ATOM 415 CA THR A 197 30.578 31.541 167.353 1.00 16.32 A ATOM 416 CB THR A 197 31.074 31.041 165.966 1.00 18.12 A ATOM 417 OG1 THR A 197 31.510 29.679 166.084 1.00 19.61 A ATOM 418 CG2 THR A 197 32.252 31.874 165.472 1.00 18.32 A ATOM 419 C THR A 197 30.006 32.967 167.262 1.00 15.64 A ATOM 420 O THR A 197 30.734 33.939 167.478 1.00 13.77 A ATOM 421 N VAL A 198 28.701 33.075 166.985 1.00 15.52 A ATOM 422 CA VAL A 198 28.006 34.372 166.908 1.00 16.32 A ATOM 423 CB VAL A 198 26.556 34.239 166.307 1.00 16.75 A ATOM 424 CG1 VAL A 198 25.839 35.597 166.262 1.00 18.00 A ATOM 425 CG2 VAL A 198 26.614 33.669 164.904 1.00 18.78 A ATOM 426 C VAL A 198 27.933 34.950 168.330 1.00 15.21 A ATOM 427 O VAL A 198 28.151 36.145 168.527 1.00 14.31 A ATOM 428 N THR A 199 27.704 34.075 169.314 1.00 14.72 A ATOM 429 CA THR A 199 27.630 34.471 170.724 1.00 15.19 A ATOM 430 CB THR A 199 27.100 33.314 171.614 1.00 16.75 A ATOM 431 OG1 THR A 199 25.810 32.914 171.141 1.00 20.05 A ATOM 432 CG2 THR A 199 26.974 33.741 173.077 1.00 15.91 A ATOM 433 C THR A 199 29.003 34.953 171.204 1.00 13.44 A ATOM 434 O THR A 199 29.086 35.970 171.889 1.00 13.34 A ATOM 435 N GLU A 200 30.071 34.281 170.758 1.00 14.14 A ATOM 436 CA GLU A 200 31.450 34.655 171.116 1.00 14.99 A ATOM 437 CB GLU A 200 32.462 33.672 170.512 1.00 15.69 A ATOM 438 CG GLU A 200 33.935 33.968 170.866 1.00 16.14 A ATOM 439 CD GLU A 200 34.906 32.871 170.452 1.00 17.37 A ATOM 440 OE1 GLU A 200 34.503 31.916 169.748 1.00 19.02 A ATOM 441 OE2 GLU A 200 36.088 32.962 170.847 1.00 18.72 A ATOM 442 C GLU A 200 31.742 36.074 170.630 1.00 15.64 A ATOM 443 O GLU A 200 32.346 36.868 171.353 1.00 14.99 A ATOM 444 N SER A 201 31.230 36.393 169.439 1.00 14.72 A ATOM 445 CA SER A 201 31.393 37.714 168.836 1.00 17.30 A ATOM 446 CB SER A 201 30.965 37.695 167.366 1.00 17.20 A ATOM 447 OG SER A 201 31.340 38.901 166.721 1.00 19.79 A ATOM 448 C SER A 201 30.589 38.763 169.586 1.00 15.73 A ATOM 449 O SER A 201 31.126 39.807 169.948 1.00 16.20 A ATOM 450 N ARG A 202 29.329 38.435 169.879 1.00 16.69 A ATOM 451 CA ARG A 202 28.413 39.326 170.595 1.00 15.65 A ATOM 452 CB ARG A 202 27.017 38.714 170.647 1.00 17.87 A ATOM 453 CG ARG A 202 26.242 38.775 169.337 1.00 19.27 A ATOM 454 CD ARG A 202 24.906 38.038 169.458 1.00 23.09 A ATOM 455 NE ARG A 202 24.133 38.461 170.629 1.00 23.59 A ATOM 456 CZ ARG A 202 23.279 39.484 170.666 1.00 25.15 A ATOM 457 NH1 ARG A 202 22.645 39.769 171.794 1.00 25.80 A ATOM 458 NH2 ARG A 202 23.048 40.217 169.586 1.00 26.28 A ATOM 459 C ARG A 202 28.883 39.659 172.009 1.00 15.85 A ATOM 460 O ARG A 202 28.764 40.804 172.445 1.00 15.35 A ATOM 461 N VAL A 203 29.448 38.665 172.701 1.00 14.75 A ATOM 462 CA VAL A 203 29.960 38.856 174.061 1.00 15.03 A ATOM 463 CB VAL A 203 30.202 37.490 174.797 1.00 13.67 A ATOM 464 CG1 VAL A 203 30.819 37.705 176.183 1.00 13.44 A ATOM 465 CG2 VAL A 203 28.877 36.761 174.969 1.00 12.74 A ATOM 466 C VAL A 203 31.225 39.723 174.015 1.00 15.83 A ATOM 467 O VAL A 203 31.351 40.651 174.802 1.00 16.91 A ATOM 468 N LEU A 204 32.100 39.478 173.037 1.00 16.93 A ATOM 469 CA LEU A 204 33.333 40.261 172.874 1.00 17.63 A ATOM 470 CB LEU A 204 34.250 39.622 171.825 1.00 17.49 A ATOM 471 CG LEU A 204 35.279 38.588 172.296 1.00 16.87 A ATOM 472 CD1 LEU A 204 35.779 37.765 171.125 1.00 16.98 A ATOM 473 CD2 LEU A 204 36.441 39.277 173.012 1.00 18.10 A ATOM 474 C LEU A 204 33.055 41.726 172.507 1.00 19.08 A ATOM 475 O LEU A 204 33.753 42.625 172.977 1.00 20.76 A ATOM 476 N GLN A 205 31.985 41.950 171.741 1.00 20.36 A ATOM 477 CA GLN A 205 31.571 43.289 171.301 1.00 23.06 A ATOM 478 CB GLN A 205 30.597 43.197 170.120 1.00 22.83 A ATOM 479 CG GLN A 205 31.162 42.674 168.821 1.00 23.09 A ATOM 480 CD GLN A 205 30.102 42.558 167.739 1.00 24.54 A ATOM 481 OE1 GLN A 205 29.446 43.541 167.386 1.00 25.94 A ATOM 482 NE2 GLN A 205 29.927 41.356 167.209 1.00 24.19 A ATOM 483 C GLN A 205 30.873 44.114 172.383 1.00 23.68 A ATOM 484 O GLN A 205 31.144 45.309 172.532 1.00 25.54 A ATOM 485 N ASN A 206 29.976 43.463 173.123 1.00 24.00 A ATOM 486 CA ASN A 206 29.167 44.117 174.151 1.00 24.37 A ATOM 487 CB ASN A 206 27.723 43.603 174.068 1.00 25.24 A ATOM 488 CG ASN A 206 27.047 43.979 172.761 1.00 26.73 A ATOM 489 OD1 ASN A 206 26.544 45.092 172.608 1.00 27.81 A ATOM 490 ND2 ASN A 206 27.054 43.058 171.804 1.00 25.36 A ATOM 491 C ASN A 206 29.643 44.134 175.604 1.00 24.23 A ATOM 492 O ASN A 206 28.905 44.593 176.485 1.00 25.66 A ATOM 493 N THR A 207 30.851 43.635 175.867 1.00 22.36 A ATOM 494 CA THR A 207 31.385 43.649 177.231 1.00 20.05 A ATOM 495 CB THR A 207 31.894 42.264 177.710 1.00 19.98 A ATOM 496 OG1 THR A 207 32.833 41.725 176.772 1.00 18.18 A ATOM 497 CG2 THR A 207 30.729 41.296 177.923 1.00 19.16 A ATOM 498 C THR A 207 32.497 44.672 177.415 1.00 19.67 A ATOM 499 O THR A 207 33.321 44.881 176.521 1.00 19.51 A ATOM 500 N ARG A 208 32.497 45.306 178.585 1.00 19.92 A ATOM 501 CA ARG A 208 33.489 46.311 178.945 1.00 20.83 A ATOM 502 CB ARG A 208 32.966 47.721 178.614 1.00 24.67 A ATOM 503 CG ARG A 208 34.001 48.651 177.973 1.00 28.29 A ATOM 504 CD ARG A 208 34.286 48.295 176.510 1.00 31.05 A ATOM 505 NE ARG A 208 33.255 48.783 175.589 1.00 32.75 A ATOM 506 CZ ARG A 208 32.748 48.089 174.569 1.00 33.94 A ATOM 507 NH1 ARG A 208 33.157 46.849 174.317 1.00 33.38 A ATOM 508 NH2 ARG A 208 31.851 48.652 173.770 1.00 34.03 A ATOM 509 C ARG A 208 33.794 46.167 180.439 1.00 19.33 A ATOM 510 O ARG A 208 33.010 46.589 181.292 1.00 19.36 A ATOM 511 N HIS A 209 34.923 45.525 180.738 1.00 17.75 A ATOM 512 CA HIS A 209 35.372 45.283 182.112 1.00 15.71 A ATOM 513 CB HIS A 209 34.744 43.975 182.634 1.00 13.97 A ATOM 514 CG HIS A 209 34.881 43.768 184.113 1.00 14.51 A ATOM 515 CD2 HIS A 209 35.808 43.099 184.838 1.00 13.07 A ATOM 516 ND1 HIS A 209 33.986 44.286 185.023 1.00 13.80 A ATOM 517 CE1 HIS A 209 34.356 43.945 186.244 1.00 13.80 A ATOM 518 NE2 HIS A 209 35.458 43.225 186.160 1.00 15.21 A ATOM 519 C HIS A 209 36.903 45.167 182.096 1.00 15.32 A ATOM 520 O HIS A 209 37.466 44.597 181.159 1.00 14.32 A ATOM 521 N PRO A 210 37.597 45.700 183.133 1.00 14.63 A ATOM 522 CD PRO A 210 37.135 46.571 184.232 1.00 15.85 A ATOM 523 CA PRO A 210 39.063 45.611 183.164 1.00 14.76 A ATOM 524 CB PRO A 210 39.427 46.386 184.434 1.00 15.04 A ATOM 525 CG PRO A 210 38.190 46.335 185.263 1.00 14.72 A ATOM 526 C PRO A 210 39.679 44.206 183.164 1.00 12.44 A ATOM 527 O PRO A 210 40.830 44.046 182.768 1.00 13.93 A ATOM 528 N PHE A 211 38.915 43.199 183.597 1.00 11.98 A ATOM 529 CA PHE A 211 39.423 41.826 183.649 1.00 11.07 A ATOM 530 CB PHE A 211 39.250 41.226 185.056 1.00 10.17 A ATOM 531 CG PHE A 211 39.810 42.097 186.148 1.00 10.42 A ATOM 532 CD1 PHE A 211 41.098 42.665 186.024 1.00 10.66 A ATOM 533 CD2 PHE A 211 39.013 42.455 187.247 1.00 11.11 A ATOM 534 CE1 PHE A 211 41.580 43.593 186.972 1.00 13.04 A ATOM 535 CE2 PHE A 211 39.482 43.380 188.210 1.00 10.99 A ATOM 536 CZ PHE A 211 40.770 43.953 188.068 1.00 11.66 A ATOM 537 C PHE A 211 38.922 40.892 182.558 1.00 10.95 A ATOM 538 O PHE A 211 39.043 39.670 182.663 1.00 11.34 A ATOM 539 N LEU A 212 38.344 41.483 181.515 1.00 10.29 A ATOM 540 CA LEU A 212 37.868 40.733 180.359 1.00 10.76 A ATOM 541 CB LEU A 212 36.357 40.910 180.141 1.00 11.36 A ATOM 542 CG LEU A 212 35.335 40.364 181.145 1.00 12.18 A ATOM 543 CD1 LEU A 212 33.963 40.658 180.631 1.00 12.06 A ATOM 544 CD2 LEU A 212 35.481 38.879 181.377 1.00 12.41 A ATOM 545 C LEU A 212 38.618 41.292 179.163 1.00 11.97 A ATOM 546 O LEU A 212 38.778 42.514 179.040 1.00 12.62 A ATOM 547 N THR A 213 39.090 40.394 178.298 1.00 11.57 A ATOM 548 CA THR A 213 39.811 40.763 177.082 1.00 12.05 A ATOM 549 CB THR A 213 40.289 39.491 176.332 1.00 13.16 A ATOM 550 OG1 THR A 213 41.159 38.743 177.188 1.00 13.29 A ATOM 551 CG2 THR A 213 41.043 39.832 175.066 1.00 13.95 A ATOM 552 C THR A 213 38.880 41.601 176.196 1.00 11.62 A ATOM 553 O THR A 213 37.741 41.209 175.940 1.00 12.81 A ATOM 554 N ALA A 214 39.348 42.797 175.841 1.00 13.78 A ATOM 555 CA ALA A 214 38.590 43.724 175.004 1.00 15.27 A ATOM 556 CB ALA A 214 38.952 45.164 175.345 1.00 16.32 A ATOM 557 C ALA A 214 38.832 43.456 173.525 1.00 15.97 A ATOM 558 O ALA A 214 39.939 43.082 173.127 1.00 15.74 A ATOM 559 N LEU A 215 37.783 43.643 172.727 1.00 15.59 A ATOM 560 CA LEU A 215 37.845 43.438 171.284 1.00 16.64 A ATOM 561 CB LEU A 215 36.554 42.775 170.787 1.00 16.49 A ATOM 562 CG LEU A 215 36.474 42.292 169.329 1.00 16.97 A ATOM 563 CD1 LEU A 215 37.284 41.017 169.148 1.00 15.18 A ATOM 564 CD2 LEU A 215 35.032 42.040 168.954 1.00 17.56 A ATOM 565 C LEU A 215 38.042 44.769 170.566 1.00 16.85 A ATOM 566 O LEU A 215 37.384 45.762 170.883 1.00 18.00 A ATOM 567 N LYS A 216 38.967 44.780 169.611 1.00 17.92 A ATOM 568 CA LYS A 216 39.248 45.969 168.816 1.00 19.21 A ATOM 569 CB LYS A 216 40.758 46.093 168.545 1.00 20.77 A ATOM 570 CG LYS A 216 41.204 47.365 167.805 1.00 24.04 A ATOM 571 CD LYS A 216 40.977 48.646 168.600 1.00 28.27 A ATOM 572 CE LYS A 216 41.317 49.872 167.762 1.00 30.49 A ATOM 573 NZ LYS A 216 40.984 51.133 168.484 1.00 34.56 A ATOM 574 C LYS A 216 38.447 45.856 167.518 1.00 19.24 A ATOM 575 O LYS A 216 37.678 46.759 167.180 1.00 20.53 A ATOM 576 N TYR A 217 38.638 44.750 166.796 1.00 19.17 A ATOM 577 CA TYR A 217 37.932 44.498 165.537 1.00 20.98 A ATOM 578 CB TYR A 217 38.835 44.717 164.306 1.00 21.08 A ATOM 579 CG TYR A 217 39.583 46.026 164.212 1.00 22.21 A ATOM 580 CD1 TYR A 217 38.897 47.258 164.131 1.00 22.98 A ATOM 581 CE1 TYR A 217 39.601 48.484 164.005 1.00 25.26 A ATOM 582 CD2 TYR A 217 40.992 46.040 164.166 1.00 23.39 A ATOM 583 CE2 TYR A 217 41.710 47.258 164.038 1.00 25.07 A ATOM 584 CZ TYR A 217 41.005 48.472 163.959 1.00 24.80 A ATOM 585 OH TYR A 217 41.691 49.656 163.845 1.00 26.66 A ATOM 586 C TYR A 217 37.424 43.065 165.441 1.00 21.24 A ATOM 587 O TYR A 217 38.001 42.140 166.012 1.00 21.28 A ATOM 588 N ALA A 218 36.329 42.906 164.709 1.00 21.97 A ATOM 589 CA ALA A 218 35.730 41.610 164.427 1.00 22.98 A ATOM 590 CB ALA A 218 34.458 41.393 165.240 1.00 22.40 A ATOM 591 C ALA A 218 35.405 41.712 162.946 1.00 23.21 A ATOM 592 O ALA A 218 34.700 42.628 162.537 1.00 23.57 A ATOM 593 N PHE A 219 36.026 40.860 162.135 1.00 24.15 A ATOM 594 CA PHE A 219 35.778 40.867 160.695 1.00 24.49 A ATOM 595 CB PHE A 219 36.751 41.821 159.947 1.00 24.79 A ATOM 596 CG PHE A 219 38.203 41.375 159.928 1.00 23.54 A ATOM 597 CD1 PHE A 219 39.064 41.680 161.000 1.00 23.92 A ATOM 598 CD2 PHE A 219 38.725 40.681 158.814 1.00 24.61 A ATOM 599 CE1 PHE A 219 40.438 41.299 160.964 1.00 22.90 A ATOM 600 CE2 PHE A 219 40.090 40.292 158.762 1.00 23.27 A ATOM 601 CZ PHE A 219 40.950 40.604 159.842 1.00 22.95 A ATOM 602 C PHE A 219 35.797 39.463 160.113 1.00 25.30 A ATOM 603 O PHE A 219 36.140 38.499 160.803 1.00 24.04 A ATOM 604 N GLN A 220 35.426 39.361 158.840 1.00 25.71 A ATOM 605 CA GLN A 220 35.403 38.085 158.142 1.00 28.27 A ATOM 606 CB GLN A 220 34.011 37.437 158.228 1.00 27.42 A ATOM 607 CG GLN A 220 32.856 38.245 157.636 1.00 27.25 A ATOM 608 CD GLN A 220 31.509 37.614 157.907 1.00 26.81 A ATOM 609 OE1 GLN A 220 31.233 36.495 157.475 1.00 25.70 A ATOM 610 NE2 GLN A 220 30.659 38.331 158.633 1.00 28.24 A ATOM 611 C GLN A 220 35.841 38.211 156.690 1.00 30.28 A ATOM 612 O GLN A 220 35.776 39.292 156.098 1.00 30.47 A ATOM 613 N THR A 221 36.359 37.105 156.161 1.00 32.45 A ATOM 614 CA THR A 221 36.799 37.008 154.772 1.00 34.77 A ATOM 615 CB THR A 221 38.307 36.634 154.660 1.00 34.88 A ATOM 616 OG1 THR A 221 38.574 35.454 155.425 1.00 34.21 A ATOM 617 CG2 THR A 221 39.198 37.779 155.140 1.00 34.18 A ATOM 618 C THR A 221 35.920 35.932 154.121 1.00 36.77 A ATOM 619 O THR A 221 34.880 35.565 154.680 1.00 37.62 A ATOM 620 N HIS A 222 36.343 35.410 152.970 1.00 38.37 A ATOM 621 CA HIS A 222 35.589 34.383 152.242 1.00 39.93 A ATOM 622 CB HIS A 222 36.071 34.305 150.788 1.00 42.29 A ATOM 623 CG HIS A 222 35.834 35.559 150.004 1.00 44.96 A ATOM 624 CD2 HIS A 222 36.684 36.348 149.304 1.00 46.37 A ATOM 625 ND1 HIS A 222 34.588 36.137 149.881 1.00 45.74 A ATOM 626 CE1 HIS A 222 34.681 37.227 149.140 1.00 47.02 A ATOM 627 NE2 HIS A 222 35.943 37.378 148.777 1.00 47.37 A ATOM 628 C HIS A 222 35.600 32.987 152.875 1.00 39.47 A ATOM 629 O HIS A 222 34.708 32.177 152.605 1.00 41.05 A ATOM 630 N ASP A 223 36.581 32.726 153.741 1.00 37.88 A ATOM 631 CA ASP A 223 36.710 31.425 154.403 1.00 36.41 A ATOM 632 CB ASP A 223 37.702 30.530 153.628 1.00 38.42 A ATOM 633 CG ASP A 223 39.125 31.093 153.601 1.00 41.14 A ATOM 634 OD1 ASP A 223 39.302 32.292 153.290 1.00 43.06 A ATOM 635 OD2 ASP A 223 40.067 30.327 153.899 1.00 42.28 A ATOM 636 C ASP A 223 37.098 31.474 155.888 1.00 34.14 A ATOM 637 O ASP A 223 37.108 30.436 156.560 1.00 33.12 A ATOM 638 N ARG A 224 37.426 32.665 156.393 1.00 31.65 A ATOM 639 CA ARG A 224 37.845 32.828 157.792 1.00 29.25 A ATOM 640 CB ARG A 224 39.353 33.133 157.862 1.00 31.08 A ATOM 641 CG ARG A 224 40.268 31.957 157.497 1.00 35.01 A ATOM 642 CD ARG A 224 41.699 32.401 157.243 1.00 38.26 A ATOM 643 NE ARG A 224 42.568 31.285 156.869 1.00 41.99 A ATOM 644 CZ ARG A 224 43.894 31.274 157.001 1.00 43.44 A ATOM 645 NH1 ARG A 224 44.537 32.324 157.504 1.00 44.06 A ATOM 646 NH2 ARG A 224 44.585 30.204 156.628 1.00 44.49 A ATOM 647 C ARG A 224 37.073 33.872 158.605 1.00 27.60 A ATOM 648 O ARG A 224 36.478 34.798 158.051 1.00 25.75 A ATOM 649 N LEU A 225 37.047 33.659 159.924 1.00 24.26 A ATOM 650 CA LEU A 225 36.403 34.551 160.897 1.00 21.38 A ATOM 651 CB LEU A 225 35.360 33.801 161.733 1.00 21.18 A ATOM 652 CG LEU A 225 34.088 33.324 161.040 1.00 21.51 A ATOM 653 CD1 LEU A 225 33.358 32.344 161.918 1.00 22.54 A ATOM 654 CD2 LEU A 225 33.212 34.501 160.686 1.00 21.44 A ATOM 655 C LEU A 225 37.523 35.027 161.808 1.00 20.15 A ATOM 656 O LEU A 225 38.254 34.205 162.367 1.00 20.04 A ATOM 657 N CYS A 226 37.644 36.343 161.974 1.00 19.07 A ATOM 658 CA CYS A 226 38.716 36.905 162.790 1.00 19.51 A ATOM 659 CB CYS A 226 39.722 37.632 161.896 1.00 19.55 A ATOM 660 SG CYS A 226 40.281 36.700 160.448 1.00 23.57 A ATOM 661 C CYS A 226 38.306 37.828 163.929 1.00 18.57 A ATOM 662 O CYS A 226 37.440 38.692 163.772 1.00 18.39 A ATOM 663 N PHE A 227 38.958 37.627 165.074 1.00 17.25 A ATOM 664 CA PHE A 227 38.752 38.423 166.283 1.00 16.14 A ATOM 665 CB PHE A 227 38.369 37.541 167.480 1.00 17.32 A ATOM 666 CG PHE A 227 37.025 36.905 167.380 1.00 17.71 A ATOM 667 CD1 PHE A 227 36.894 35.513 167.524 1.00 17.96 A ATOM 668 CD2 PHE A 227 35.873 37.685 167.186 1.00 18.00 A ATOM 669 CE1 PHE A 227 35.621 34.892 167.483 1.00 19.19 A ATOM 670 CE2 PHE A 227 34.605 37.084 167.144 1.00 19.33 A ATOM 671 CZ PHE A 227 34.472 35.680 167.295 1.00 18.55 A ATOM 672 C PHE A 227 40.074 39.090 166.627 1.00 15.62 A ATOM 673 O PHE A 227 41.033 38.405 166.973 1.00 15.83 A ATOM 674 N VAL A 228 40.127 40.415 166.533 1.00 15.49 A ATOM 675 CA VAL A 228 41.340 41.165 166.863 1.00 15.30 A ATOM 676 CB VAL A 228 41.592 42.323 165.850 1.00 15.49 A ATOM 677 CG1 VAL A 228 42.885 43.040 166.151 1.00 14.57 A ATOM 678 CG2 VAL A 228 41.640 41.785 164.435 1.00 18.30 A ATOM 679 C VAL A 228 41.131 41.670 168.294 1.00 14.86 A ATOM 680 O VAL A 228 40.414 42.644 168.538 1.00 14.24 A ATOM 681 N MET A 229 41.705 40.927 169.236 1.00 15.11 A ATOM 682 CA MET A 229 41.594 41.212 170.666 1.00 15.13 A ATOM 683 CB MET A 229 41.430 39.902 171.437 1.00 14.74 A ATOM 684 CG MET A 229 40.387 38.940 170.934 1.00 17.80 A ATOM 685 SD MET A 229 40.569 37.400 171.834 1.00 19.60 A ATOM 686 CE MET A 229 41.938 36.649 170.952 1.00 16.89 A ATOM 687 C MET A 229 42.846 41.873 171.212 1.00 15.65 A ATOM 688 O MET A 229 43.904 41.805 170.589 1.00 16.17 A ATOM 689 N GLU A 230 42.740 42.450 172.413 1.00 15.75 A ATOM 690 CA GLU A 230 43.900 43.052 173.067 1.00 17.42 A ATOM 691 CB GLU A 230 43.504 43.950 174.256 1.00 20.56 A ATOM 692 CG GLU A 230 42.870 43.263 175.453 1.00 24.89 A ATOM 693 CD GLU A 230 42.589 44.204 176.615 1.00 26.43 A ATOM 694 OE1 GLU A 230 43.444 45.060 176.940 1.00 29.81 A ATOM 695 OE2 GLU A 230 41.510 44.069 177.224 1.00 22.46 A ATOM 696 C GLU A 230 44.825 41.896 173.489 1.00 16.10 A ATOM 697 O GLU A 230 44.360 40.816 173.891 1.00 15.53 A ATOM 698 N TYR A 231 46.116 42.099 173.269 1.00 14.61 A ATOM 699 CA TYR A 231 47.143 41.109 173.562 1.00 14.63 A ATOM 700 CB TYR A 231 48.372 41.399 172.679 1.00 15.21 A ATOM 701 CG TYR A 231 49.619 40.562 172.903 1.00 15.22 A ATOM 702 CD1 TYR A 231 49.560 39.151 172.979 1.00 15.64 A ATOM 703 CE1 TYR A 231 50.734 38.378 173.188 1.00 17.96 A ATOM 704 CD2 TYR A 231 50.877 41.182 173.033 1.00 15.49 A ATOM 705 CE2 TYR A 231 52.060 40.415 173.236 1.00 16.52 A ATOM 706 CZ TYR A 231 51.976 39.020 173.314 1.00 16.37 A ATOM 707 OH TYR A 231 53.110 38.274 173.527 1.00 18.34 A ATOM 708 C TYR A 231 47.515 41.041 175.042 1.00 14.32 A ATOM 709 O TYR A 231 47.859 42.051 175.657 1.00 15.12 A ATOM 710 N ALA A 232 47.433 39.829 175.592 1.00 13.08 A ATOM 711 CA ALA A 232 47.788 39.572 176.982 1.00 12.20 A ATOM 712 CB ALA A 232 46.844 38.556 177.582 1.00 11.96 A ATOM 713 C ALA A 232 49.237 39.067 177.007 1.00 13.00 A ATOM 714 O ALA A 232 49.496 37.863 176.882 1.00 11.98 A ATOM 715 N ASN A 233 50.163 40.018 177.172 1.00 12.50 A ATOM 716 CA ASN A 233 51.619 39.793 177.193 1.00 14.35 A ATOM 717 CB ASN A 233 52.365 41.114 177.438 1.00 14.72 A ATOM 718 CG ASN A 233 52.082 42.164 176.387 1.00 18.13 A ATOM 719 OD1 ASN A 233 52.952 42.495 175.577 1.00 18.88 A ATOM 720 ND2 ASN A 233 50.868 42.705 176.398 1.00 17.15 A ATOM 721 C ASN A 233 52.124 38.794 178.225 1.00 12.73 A ATOM 722 O ASN A 233 53.154 38.139 178.019 1.00 13.87 A ATOM 723 N GLY A 234 51.392 38.695 179.332 1.00 12.52 A ATOM 724 CA GLY A 234 51.768 37.812 180.420 1.00 11.86 A ATOM 725 C GLY A 234 51.504 36.332 180.298 1.00 11.18 A ATOM 726 O GLY A 234 51.895 35.584 181.188 1.00 12.45 A ATOM 727 N GLY A 235 50.850 35.902 179.221 1.00 11.65 A ATOM 728 CA GLY A 235 50.576 34.484 179.034 1.00 12.03 A ATOM 729 C GLY A 235 49.470 33.931 179.914 1.00 11.49 A ATOM 730 O GLY A 235 48.814 34.674 180.647 1.00 12.06 A ATOM 731 N GLU A 236 49.279 32.616 179.840 1.00 10.95 A ATOM 732 CA GLU A 236 48.244 31.914 180.598 1.00 10.55 A ATOM 733 CB GLU A 236 48.008 30.521 180.019 1.00 11.33 A ATOM 734 CG GLU A 236 47.733 30.443 178.540 1.00 12.01 A ATOM 735 CD GLU A 236 47.744 29.013 178.016 1.00 13.60 A ATOM 736 OE1 GLU A 236 48.240 28.101 178.715 1.00 13.29 A ATOM 737 OE2 GLU A 236 47.244 28.792 176.898 1.00 13.08 A ATOM 738 C GLU A 236 48.638 31.718 182.046 1.00 9.40 A ATOM 739 O GLU A 236 49.820 31.612 182.367 1.00 9.30 A ATOM 740 N LEU A 237 47.631 31.581 182.908 1.00 10.59 A ATOM 741 CA LEU A 237 47.860 31.324 184.326 1.00 12.01 A ATOM 742 CB LEU A 237 46.546 31.464 185.102 1.00 13.34 A ATOM 743 CG LEU A 237 46.561 32.014 186.534 1.00 17.84 A ATOM 744 CD1 LEU A 237 47.318 33.336 186.615 1.00 17.25 A ATOM 745 CD2 LEU A 237 45.121 32.199 187.007 1.00 14.63 A ATOM 746 C LEU A 237 48.421 29.897 184.417 1.00 10.85 A ATOM 747 O LEU A 237 49.205 29.584 185.310 1.00 11.83 A ATOM 748 N PHE A 238 48.093 29.092 183.399 1.00 10.15 A ATOM 749 CA PHE A 238 48.553 27.706 183.250 1.00 10.40 A ATOM 750 CB PHE A 238 47.860 27.054 182.035 1.00 11.19 A ATOM 751 CG PHE A 238 48.218 25.600 181.811 1.00 15.22 A ATOM 752 CD1 PHE A 238 48.063 24.641 182.836 1.00 17.28 A ATOM 753 CD2 PHE A 238 48.736 25.188 180.569 1.00 15.71 A ATOM 754 CE1 PHE A 238 48.428 23.283 182.624 1.00 17.50 A ATOM 755 CE2 PHE A 238 49.103 23.834 180.340 1.00 17.73 A ATOM 756 CZ PHE A 238 48.949 22.880 181.373 1.00 17.04 A ATOM 757 C PHE A 238 50.076 27.643 183.100 1.00 10.74 A ATOM 758 O PHE A 238 50.711 26.766 183.685 1.00 10.07 A ATOM 759 N PHE A 239 50.652 28.589 182.353 1.00 9.77 A ATOM 760 CA PHE A 239 52.104 28.647 182.147 1.00 10.45 A ATOM 761 CB PHE A 239 52.469 29.757 181.134 1.00 11.60 A ATOM 762 CG PHE A 239 53.926 29.757 180.719 1.00 12.43 A ATOM 763 CD1 PHE A 239 54.367 28.925 179.673 1.00 12.74 A ATOM 764 CD2 PHE A 239 54.877 30.545 181.410 1.00 10.98 A ATOM 765 CE1 PHE A 239 55.745 28.866 179.315 1.00 16.02 A ATOM 766 CE2 PHE A 239 56.259 30.496 181.068 1.00 14.21 A ATOM 767 CZ PHE A 239 56.691 29.654 180.019 1.00 14.99 A ATOM 768 C PHE A 239 52.824 28.899 183.475 1.00 10.20 A ATOM 769 O PHE A 239 53.789 28.202 183.810 1.00 9.58 A ATOM 770 N HIS A 240 52.329 29.888 184.219 1.00 9.88 A ATOM 771 CA HIS A 240 52.901 30.290 185.503 1.00 11.98 A ATOM 772 CB HIS A 240 52.319 31.632 185.944 1.00 12.15 A ATOM 773 CG HIS A 240 52.584 32.736 184.974 1.00 12.41 A ATOM 774 CD2 HIS A 240 51.770 33.362 184.094 1.00 12.25 A ATOM 775 ND1 HIS A 240 53.836 33.282 184.796 1.00 12.84 A ATOM 776 CE1 HIS A 240 53.780 34.196 183.844 1.00 13.59 A ATOM 777 NE2 HIS A 240 52.539 34.264 183.402 1.00 12.96 A ATOM 778 C HIS A 240 52.751 29.254 186.599 1.00 11.94 A ATOM 779 O HIS A 240 53.708 28.989 187.327 1.00 13.30 A ATOM 780 N LEU A 241 51.571 28.634 186.676 1.00 13.96 A ATOM 781 CA LEU A 241 51.308 27.608 187.681 1.00 12.92 A ATOM 782 CB LEU A 241 49.805 27.335 187.818 1.00 14.05 A ATOM 783 CG LEU A 241 49.351 26.532 189.043 1.00 13.77 A ATOM 784 CD1 LEU A 241 49.746 27.213 190.344 1.00 14.38 A ATOM 785 CD2 LEU A 241 47.874 26.374 188.981 1.00 13.17 A ATOM 786 C LEU A 241 52.080 26.318 187.414 1.00 14.44 A ATOM 787 O LEU A 241 52.565 25.698 188.356 1.00 14.08 A ATOM 788 N SER A 242 52.242 25.956 186.138 1.00 13.96 A ATOM 789 CA SER A 242 52.996 24.756 185.753 1.00 15.59 A ATOM 790 CB SER A 242 52.880 24.489 184.249 1.00 16.20 A ATOM 791 OG SER A 242 51.543 24.187 183.880 1.00 18.65 A ATOM 792 C SER A 242 54.472 24.907 186.131 1.00 16.05 A ATOM 793 O SER A 242 55.104 23.946 186.561 1.00 17.31 A ATOM 794 N ARG A 243 54.980 26.137 186.017 1.00 14.31 A ATOM 795 CA ARG A 243 56.369 26.481 186.344 1.00 14.86 A ATOM 796 CB ARG A 243 56.729 27.836 185.700 1.00 15.08 A ATOM 797 CG ARG A 243 58.152 28.360 185.968 1.00 16.55 A ATOM 798 CD ARG A 243 58.311 29.821 185.540 1.00 17.96 A ATOM 799 NE ARG A 243 57.546 30.745 186.384 1.00 21.78 A ATOM 800 CZ ARG A 243 56.771 31.731 185.929 1.00 22.92 A ATOM 801 NH1 ARG A 243 56.638 31.947 184.626 1.00 23.68 A ATOM 802 NH2 ARG A 243 56.112 32.501 186.785 1.00 24.74 A ATOM 803 C ARG A 243 56.608 26.545 187.860 1.00 14.72 A ATOM 804 O ARG A 243 57.531 25.907 188.378 1.00 14.26 A ATOM 805 N GLU A 244 55.755 27.296 188.556 1.00 12.67 A ATOM 806 CA GLU A 244 55.861 27.497 190.002 1.00 13.25 A ATOM 807 CB GLU A 244 55.263 28.853 190.383 1.00 15.29 A ATOM 808 CG GLU A 244 55.997 30.046 189.774 1.00 20.11 A ATOM 809 CD GLU A 244 55.456 31.381 190.245 1.00 22.00 A ATOM 810 OE1 GLU A 244 55.241 31.553 191.465 1.00 25.13 A ATOM 811 OE2 GLU A 244 55.258 32.273 189.395 1.00 26.82 A ATOM 812 C GLU A 244 55.262 26.403 190.889 1.00 12.35 A ATOM 813 O GLU A 244 55.461 26.426 192.106 1.00 12.06 A ATOM 814 N ARG A 245 54.592 25.424 190.263 1.00 12.65 A ATOM 815 CA ARG A 245 53.913 24.267 190.905 1.00 12.33 A ATOM 816 CB ARG A 245 54.856 23.388 191.767 1.00 15.96 A ATOM 817 CG ARG A 245 56.232 23.022 191.185 1.00 17.57 A ATOM 818 CD ARG A 245 56.190 22.359 189.828 1.00 19.78 A ATOM 819 NE ARG A 245 57.537 21.940 189.445 1.00 21.49 A ATOM 820 CZ ARG A 245 58.108 22.172 188.266 1.00 22.07 A ATOM 821 NH1 ARG A 245 57.464 22.834 187.314 1.00 21.19 A ATOM 822 NH2 ARG A 245 59.326 21.705 188.031 1.00 23.54 A ATOM 823 C ARG A 245 52.689 24.634 191.750 1.00 12.77 A ATOM 824 O ARG A 245 51.650 23.970 191.667 1.00 11.62 A ATOM 825 N VAL A 246 52.830 25.678 192.566 1.00 10.78 A ATOM 826 CA VAL A 246 51.777 26.148 193.467 1.00 11.80 A ATOM 827 CB VAL A 246 51.771 25.295 194.799 1.00 12.61 A ATOM 828 CG1 VAL A 246 53.016 25.563 195.654 1.00 12.86 A ATOM 829 CG2 VAL A 246 50.494 25.503 195.587 1.00 12.03 A ATOM 830 C VAL A 246 51.968 27.641 193.774 1.00 11.54 A ATOM 831 O VAL A 246 53.090 28.150 193.727 1.00 11.04 A ATOM 832 N PHE A 247 50.862 28.337 194.046 1.00 11.44 A ATOM 833 CA PHE A 247 50.897 29.758 194.394 1.00 11.43 A ATOM 834 CB PHE A 247 49.806 30.559 193.654 1.00 10.98 A ATOM 835 CG PHE A 247 50.010 30.702 192.162 1.00 10.69 A ATOM 836 CD1 PHE A 247 51.282 30.578 191.558 1.00 9.91 A ATOM 837 CD2 PHE A 247 48.903 31.004 191.345 1.00 10.05 A ATOM 838 CE1 PHE A 247 51.448 30.757 190.152 1.00 10.67 A ATOM 839 CE2 PHE A 247 49.047 31.184 189.940 1.00 10.23 A ATOM 840 CZ PHE A 247 50.325 31.061 189.343 1.00 9.00 A ATOM 841 C PHE A 247 50.600 29.876 195.880 1.00 11.50 A ATOM 842 O PHE A 247 49.991 28.978 196.473 1.00 11.11 A ATOM 843 N THR A 248 51.008 30.998 196.477 1.00 12.66 A ATOM 844 CA THR A 248 50.719 31.261 197.888 1.00 12.42 A ATOM 845 CB THR A 248 51.525 32.465 198.439 1.00 12.30 A ATOM 846 OG1 THR A 248 51.186 33.650 197.709 1.00 13.52 A ATOM 847 CG2 THR A 248 53.025 32.209 198.329 1.00 14.93 A ATOM 848 C THR A 248 49.229 31.607 197.950 1.00 12.03 A ATOM 849 O THR A 248 48.615 31.915 196.917 1.00 13.38 A ATOM 850 N GLU A 249 48.655 31.563 199.146 1.00 12.55 A ATOM 851 CA GLU A 249 47.241 31.874 199.327 1.00 12.92 A ATOM 852 CB GLU A 249 46.794 31.513 200.734 1.00 13.33 A ATOM 853 CG GLU A 249 46.767 30.009 200.966 1.00 15.98 A ATOM 854 CD GLU A 249 46.055 29.624 202.235 1.00 15.69 A ATOM 855 OE1 GLU A 249 45.152 30.378 202.665 1.00 15.93 A ATOM 856 OE2 GLU A 249 46.390 28.559 202.801 1.00 13.53 A ATOM 857 C GLU A 249 46.895 33.323 199.000 1.00 12.47 A ATOM 858 O GLU A 249 45.829 33.590 198.451 1.00 11.25 A ATOM 859 N GLU A 250 47.844 34.231 199.245 1.00 13.16 A ATOM 860 CA GLU A 250 47.657 35.654 198.969 1.00 14.49 A ATOM 861 CB GLU A 250 48.710 36.500 199.705 1.00 19.43 A ATOM 862 CG GLU A 250 48.371 37.999 199.834 1.00 26.02 A ATOM 863 CD GLU A 250 47.109 38.267 200.658 1.00 28.19 A ATOM 864 OE1 GLU A 250 47.137 38.051 201.889 1.00 33.54 A ATOM 865 OE2 GLU A 250 46.091 38.692 200.072 1.00 28.94 A ATOM 866 C GLU A 250 47.698 35.924 197.463 1.00 13.59 A ATOM 867 O GLU A 250 46.941 36.762 196.958 1.00 12.85 A ATOM 868 N ARG A 251 48.542 35.173 196.750 1.00 12.93 A ATOM 869 CA ARG A 251 48.669 35.315 195.299 1.00 11.46 A ATOM 870 CB ARG A 251 49.937 34.628 194.778 1.00 13.58 A ATOM 871 CG ARG A 251 50.109 34.767 193.274 1.00 14.49 A ATOM 872 CD ARG A 251 51.522 34.658 192.796 1.00 18.51 A ATOM 873 NE ARG A 251 51.563 34.773 191.340 1.00 19.55 A ATOM 874 CZ ARG A 251 52.558 34.333 190.578 1.00 20.55 A ATOM 875 NH1 ARG A 251 53.611 33.749 191.128 1.00 23.76 A ATOM 876 NH2 ARG A 251 52.490 34.459 189.260 1.00 22.77 A ATOM 877 C ARG A 251 47.418 34.755 194.615 1.00 10.01 A ATOM 878 O ARG A 251 46.904 35.352 193.666 1.00 10.64 A ATOM 879 N ALA A 252 46.908 33.647 195.150 1.00 10.04 A ATOM 880 CA ALA A 252 45.698 33.010 194.632 1.00 10.06 A ATOM 881 CB ALA A 252 45.517 31.660 195.252 1.00 12.46 A ATOM 882 C ALA A 252 44.480 33.889 194.907 1.00 10.61 A ATOM 883 O ALA A 252 43.577 33.976 194.071 1.00 8.88 A ATOM 884 N ARG A 253 44.505 34.594 196.046 1.00 9.47 A ATOM 885 CA ARG A 253 43.428 35.507 196.446 1.00 10.22 A ATOM 886 CB ARG A 253 43.654 36.009 197.880 1.00 11.58 A ATOM 887 CG ARG A 253 42.640 37.044 198.395 1.00 15.79 A ATOM 888 CD ARG A 253 42.515 37.073 199.916 1.00 18.19 A ATOM 889 NE ARG A 253 43.780 36.884 200.615 1.00 21.67 A ATOM 890 CZ ARG A 253 44.006 35.940 201.527 1.00 21.38 A ATOM 891 NH1 ARG A 253 43.048 35.086 201.874 1.00 22.53 A ATOM 892 NH2 ARG A 253 45.215 35.814 202.044 1.00 24.22 A ATOM 893 C ARG A 253 43.319 36.685 195.481 1.00 9.40 A ATOM 894 O ARG A 253 42.215 37.081 195.109 1.00 8.31 A ATOM 895 N PHE A 254 44.471 37.194 195.044 1.00 9.39 A ATOM 896 CA PHE A 254 44.526 38.311 194.103 1.00 9.66 A ATOM 897 CB PHE A 254 45.977 38.773 193.879 1.00 9.36 A ATOM 898 CG PHE A 254 46.108 39.931 192.911 1.00 11.36 A ATOM 899 CD1 PHE A 254 45.963 41.255 193.362 1.00 15.23 A ATOM 900 CD2 PHE A 254 46.339 39.700 191.531 1.00 15.03 A ATOM 901 CE1 PHE A 254 46.040 42.345 192.454 1.00 16.82 A ATOM 902 CE2 PHE A 254 46.418 40.776 190.609 1.00 15.10 A ATOM 903 CZ PHE A 254 46.266 42.103 191.078 1.00 16.06 A ATOM 904 C PHE A 254 43.878 37.921 192.770 1.00 8.48 A ATOM 905 O PHE A 254 43.020 38.643 192.272 1.00 8.74 A ATOM 906 N TYR A 255 44.311 36.793 192.202 1.00 8.89 A ATOM 907 CA TYR A 255 43.774 36.306 190.928 1.00 9.03 A ATOM 908 CB TYR A 255 44.590 35.121 190.396 1.00 9.19 A ATOM 909 CG TYR A 255 46.029 35.450 190.040 1.00 9.91 A ATOM 910 CD1 TYR A 255 46.377 36.685 189.445 1.00 9.09 A ATOM 911 CE1 TYR A 255 47.731 37.000 189.129 1.00 9.66 A ATOM 912 CD2 TYR A 255 47.061 34.531 190.309 1.00 9.65 A ATOM 913 CE2 TYR A 255 48.421 34.834 189.988 1.00 9.49 A ATOM 914 CZ TYR A 255 48.740 36.069 189.403 1.00 11.34 A ATOM 915 OH TYR A 255 50.052 36.368 189.105 1.00 11.59 A ATOM 916 C TYR A 255 42.308 35.925 191.055 1.00 7.99 A ATOM 917 O TYR A 255 41.498 36.312 190.218 1.00 7.50 A ATOM 918 N GLY A 256 41.975 35.259 192.163 1.00 8.47 A ATOM 919 CA GLY A 256 40.608 34.845 192.440 1.00 7.94 A ATOM 920 C GLY A 256 39.651 36.017 192.548 1.00 7.98 A ATOM 921 O GLY A 256 38.563 35.969 191.977 1.00 7.43 A ATOM 922 N ALA A 257 40.102 37.101 193.190 1.00 8.64 A ATOM 923 CA ALA A 257 39.296 38.316 193.354 1.00 9.93 A ATOM 924 CB ALA A 257 39.993 39.306 194.276 1.00 10.11 A ATOM 925 C ALA A 257 38.985 38.977 192.015 1.00 10.56 A ATOM 926 O ALA A 257 37.859 39.420 191.773 1.00 10.25 A ATOM 927 N GLU A 258 39.971 38.971 191.121 1.00 10.39 A ATOM 928 CA GLU A 258 39.794 39.558 189.800 1.00 11.25 A ATOM 929 CB GLU A 258 41.146 39.820 189.138 1.00 11.50 A ATOM 930 CG GLU A 258 42.025 40.767 189.944 1.00 10.66 A ATOM 931 CD GLU A 258 43.165 41.375 189.153 1.00 14.47 A ATOM 932 OE1 GLU A 258 43.711 40.715 188.252 1.00 13.36 A ATOM 933 OE2 GLU A 258 43.517 42.542 189.431 1.00 15.92 A ATOM 934 C GLU A 258 38.863 38.722 188.914 1.00 10.08 A ATOM 935 O GLU A 258 38.052 39.285 188.174 1.00 9.82 A ATOM 936 N ILE A 259 38.904 37.393 189.082 1.00 10.00 A ATOM 937 CA ILE A 259 38.040 36.468 188.326 1.00 9.66 A ATOM 938 CB ILE A 259 38.498 34.977 188.450 1.00 9.87 A ATOM 939 CG2 ILE A 259 37.526 34.033 187.700 1.00 8.88 A ATOM 940 CG1 ILE A 259 39.893 34.803 187.839 1.00 11.12 A ATOM 941 CD1 ILE A 259 40.627 33.550 188.318 1.00 12.02 A ATOM 942 C ILE A 259 36.594 36.615 188.819 1.00 9.65 A ATOM 943 O ILE A 259 35.672 36.645 188.003 1.00 9.15 A ATOM 944 N VAL A 260 36.417 36.759 190.139 1.00 8.61 A ATOM 945 CA VAL A 260 35.087 36.934 190.754 1.00 8.52 A ATOM 946 CB VAL A 260 35.161 36.963 192.314 1.00 7.63 A ATOM 947 CG1 VAL A 260 33.801 37.292 192.931 1.00 8.09 A ATOM 948 CG2 VAL A 260 35.615 35.622 192.847 1.00 7.58 A ATOM 949 C VAL A 260 34.451 38.232 190.242 1.00 9.95 A ATOM 950 O VAL A 260 33.272 38.247 189.887 1.00 9.77 A ATOM 951 N SER A 261 35.259 39.292 190.165 1.00 10.95 A ATOM 952 CA SER A 261 34.818 40.605 189.680 1.00 10.64 A ATOM 953 CB SER A 261 35.967 41.614 189.793 1.00 12.26 A ATOM 954 OG SER A 261 35.595 42.886 189.298 1.00 13.27 A ATOM 955 C SER A 261 34.333 40.505 188.228 1.00 10.64 A ATOM 956 O SER A 261 33.264 41.018 187.889 1.00 10.21 A ATOM 957 N ALA A 262 35.082 39.757 187.416 1.00 9.57 A ATOM 958 CA ALA A 262 34.764 39.533 186.005 1.00 10.66 A ATOM 959 CB ALA A 262 35.937 38.891 185.309 1.00 9.52 A ATOM 960 C ALA A 262 33.512 38.672 185.834 1.00 10.95 A ATOM 961 O ALA A 262 32.673 38.958 184.978 1.00 11.45 A ATOM 962 N LEU A 263 33.378 37.647 186.678 1.00 10.72 A ATOM 963 CA LEU A 263 32.221 36.746 186.643 1.00 8.95 A ATOM 964 CB LEU A 263 32.505 35.456 187.419 1.00 9.12 A ATOM 965 CG LEU A 263 33.369 34.389 186.731 1.00 8.06 A ATOM 966 CD1 LEU A 263 33.638 33.255 187.709 1.00 7.97 A ATOM 967 CD2 LEU A 263 32.689 33.851 185.479 1.00 8.44 A ATOM 968 C LEU A 263 30.942 37.421 187.139 1.00 10.52 A ATOM 969 O LEU A 263 29.859 37.151 186.615 1.00 9.90 A ATOM 970 N GLU A 264 31.091 38.349 188.091 1.00 10.31 A ATOM 971 CA GLU A 264 29.973 39.131 188.646 1.00 11.96 A ATOM 972 CB GLU A 264 30.466 40.041 189.793 1.00 14.48 A ATOM 973 CG GLU A 264 29.376 40.752 190.653 1.00 20.37 A ATOM 974 CD GLU A 264 28.795 42.031 190.049 1.00 24.02 A ATOM 975 OE1 GLU A 264 27.588 42.287 190.257 1.00 26.91 A ATOM 976 OE2 GLU A 264 29.532 42.771 189.363 1.00 26.95 A ATOM 977 C GLU A 264 29.425 39.997 187.515 1.00 11.34 A ATOM 978 O GLU A 264 28.211 40.066 187.316 1.00 10.55 A ATOM 979 N TYR A 265 30.341 40.645 186.790 1.00 11.64 A ATOM 980 CA TYR A 265 29.999 41.514 185.667 1.00 11.05 A ATOM 981 CB TYR A 265 31.252 42.212 185.108 1.00 12.33 A ATOM 982 CG TYR A 265 31.010 43.028 183.843 1.00 12.95 A ATOM 983 CD1 TYR A 265 30.414 44.310 183.902 1.00 13.79 A ATOM 984 CE1 TYR A 265 30.107 45.029 182.711 1.00 13.88 A ATOM 985 CD2 TYR A 265 31.300 42.485 182.573 1.00 12.24 A ATOM 986 CE2 TYR A 265 30.997 43.189 181.385 1.00 14.47 A ATOM 987 CZ TYR A 265 30.402 44.453 181.462 1.00 15.05 A ATOM 988 OH TYR A 265 30.102 45.110 180.294 1.00 15.45 A ATOM 989 C TYR A 265 29.278 40.734 184.565 1.00 10.82 A ATOM 990 O TYR A 265 28.272 41.206 184.046 1.00 12.32 A ATOM 991 N LEU A 266 29.816 39.566 184.207 1.00 11.18 A ATOM 992 CA LEU A 266 29.221 38.716 183.170 1.00 10.85 A ATOM 993 CB LEU A 266 30.115 37.510 182.867 1.00 11.40 A ATOM 994 CG LEU A 266 31.366 37.737 182.007 1.00 10.46 A ATOM 995 CD1 LEU A 266 32.222 36.476 182.001 1.00 11.44 A ATOM 996 CD2 LEU A 266 30.983 38.117 180.577 1.00 12.01 A ATOM 997 C LEU A 266 27.813 38.256 183.548 1.00 10.96 A ATOM 998 O LEU A 266 26.889 38.385 182.746 1.00 9.27 A ATOM 999 N HIS A 267 27.644 37.807 184.794 1.00 9.75 A ATOM 1000 CA HIS A 267 26.345 37.350 185.292 1.00 10.52 A ATOM 1001 CB HIS A 267 26.488 36.649 186.652 1.00 10.88 A ATOM 1002 CG HIS A 267 27.144 35.298 186.585 1.00 9.28 A ATOM 1003 CD2 HIS A 267 27.781 34.655 185.575 1.00 9.90 A ATOM 1004 ND1 HIS A 267 27.185 34.441 187.664 1.00 10.19 A ATOM 1005 CE1 HIS A 267 27.814 33.332 187.324 1.00 10.55 A ATOM 1006 NE2 HIS A 267 28.186 33.436 186.062 1.00 10.79 A ATOM 1007 C HIS A 267 25.315 38.484 185.371 1.00 11.93 A ATOM 1008 O HIS A 267 24.127 38.247 185.155 1.00 14.31 A ATOM 1009 N SER A 268 25.793 39.715 185.586 1.00 12.99 A ATOM 1010 CA SER A 268 24.932 40.906 185.666 1.00 16.08 A ATOM 1011 CB SER A 268 25.654 42.063 186.377 1.00 14.97 A ATOM 1012 OG SER A 268 26.632 42.678 185.554 1.00 19.70 A ATOM 1013 C SER A 268 24.454 41.343 184.271 1.00 17.40 A ATOM 1014 O SER A 268 23.441 42.034 184.138 1.00 19.73 A ATOM 1015 N ARG A 269 25.196 40.914 183.246 1.00 17.18 A ATOM 1016 CA ARG A 269 24.888 41.193 181.841 1.00 17.62 A ATOM 1017 CB ARG A 269 26.177 41.498 181.060 1.00 21.11 A ATOM 1018 CG ARG A 269 26.888 42.795 181.454 1.00 25.38 A ATOM 1019 CD ARG A 269 26.203 44.039 180.904 1.00 27.78 A ATOM 1020 NE ARG A 269 26.350 44.157 179.453 1.00 32.09 A ATOM 1021 CZ ARG A 269 25.748 45.076 178.699 1.00 33.70 A ATOM 1022 NH1 ARG A 269 24.939 45.979 179.244 1.00 34.89 A ATOM 1023 NH2 ARG A 269 25.963 45.097 177.391 1.00 33.61 A ATOM 1024 C ARG A 269 24.175 39.977 181.227 1.00 16.92 A ATOM 1025 O ARG A 269 24.036 39.872 180.000 1.00 16.31 A ATOM 1026 N ASP A 270 23.724 39.074 182.107 1.00 14.40 A ATOM 1027 CA ASP A 270 23.005 37.830 181.778 1.00 13.46 A ATOM 1028 CB ASP A 270 21.650 38.124 181.092 1.00 14.60 A ATOM 1029 CG ASP A 270 20.732 39.018 181.925 1.00 18.26 A ATOM 1030 OD1 ASP A 270 20.919 39.132 183.158 1.00 18.04 A ATOM 1031 OD2 ASP A 270 19.802 39.605 181.331 1.00 21.02 A ATOM 1032 C ASP A 270 23.815 36.808 180.964 1.00 11.78 A ATOM 1033 O ASP A 270 23.257 36.012 180.199 1.00 10.83 A ATOM 1034 N VAL A 271 25.131 36.817 181.167 1.00 10.42 A ATOM 1035 CA VAL A 271 26.043 35.920 180.457 1.00 9.27 A ATOM 1036 CB VAL A 271 27.173 36.721 179.713 1.00 10.84 A ATOM 1037 CG1 VAL A 271 28.106 35.785 178.950 1.00 11.06 A ATOM 1038 CG2 VAL A 271 26.575 37.749 178.751 1.00 10.78 A ATOM 1039 C VAL A 271 26.700 34.919 181.408 1.00 9.33 A ATOM 1040 O VAL A 271 27.217 35.297 182.457 1.00 10.42 A ATOM 1041 N VAL A 272 26.643 33.641 181.033 1.00 7.94 A ATOM 1042 CA VAL A 272 27.279 32.561 181.790 1.00 6.49 A ATOM 1043 CB VAL A 272 26.308 31.377 182.034 1.00 6.42 A ATOM 1044 CG1 VAL A 272 26.991 30.243 182.811 1.00 8.22 A ATOM 1045 CG2 VAL A 272 25.153 31.861 182.833 1.00 6.79 A ATOM 1046 C VAL A 272 28.463 32.152 180.915 1.00 7.17 A ATOM 1047 O VAL A 272 28.299 31.860 179.728 1.00 8.47 A ATOM 1048 N TYR A 273 29.646 32.132 181.522 1.00 6.61 A ATOM 1049 CA TYR A 273 30.895 31.827 180.830 1.00 8.02 A ATOM 1050 CB TYR A 273 32.048 32.422 181.648 1.00 7.65 A ATOM 1051 CG TYR A 273 33.395 32.332 181.000 1.00 7.99 A ATOM 1052 CD1 TYR A 273 33.727 33.105 179.865 1.00 7.18 A ATOM 1053 CE1 TYR A 273 34.985 32.949 179.229 1.00 6.85 A ATOM 1054 CD2 TYR A 273 34.338 31.430 181.485 1.00 7.03 A ATOM 1055 CE2 TYR A 273 35.576 31.280 180.871 1.00 8.23 A ATOM 1056 CZ TYR A 273 35.896 32.020 179.755 1.00 6.72 A ATOM 1057 OH TYR A 273 37.112 31.765 179.196 1.00 8.95 A ATOM 1058 C TYR A 273 31.125 30.351 180.437 1.00 9.03 A ATOM 1059 O TYR A 273 31.582 30.077 179.322 1.00 8.84 A ATOM 1060 N ARG A 274 30.864 29.428 181.369 1.00 8.63 A ATOM 1061 CA ARG A 274 30.977 27.967 181.173 1.00 9.18 A ATOM 1062 CB ARG A 274 29.961 27.463 180.122 1.00 9.26 A ATOM 1063 CG ARG A 274 28.505 27.591 180.537 1.00 10.03 A ATOM 1064 CD ARG A 274 27.570 26.835 179.606 1.00 10.31 A ATOM 1065 NE ARG A 274 27.509 27.402 178.258 1.00 10.13 A ATOM 1066 CZ ARG A 274 26.604 27.069 177.337 1.00 10.15 A ATOM 1067 NH1 ARG A 274 25.670 26.164 177.602 1.00 10.43 A ATOM 1068 NH2 ARG A 274 26.623 27.660 176.151 1.00 8.58 A ATOM 1069 C ARG A 274 32.331 27.292 180.912 1.00 9.34 A ATOM 1070 O ARG A 274 32.408 26.059 180.946 1.00 11.86 A ATOM 1071 N ASP A 275 33.390 28.066 180.679 1.00 8.02 A ATOM 1072 CA ASP A 275 34.693 27.459 180.402 1.00 8.04 A ATOM 1073 CB ASP A 275 34.995 27.532 178.886 1.00 9.80 A ATOM 1074 CG ASP A 275 36.035 26.501 178.433 1.00 7.91 A ATOM 1075 OD1 ASP A 275 36.271 25.518 179.166 1.00 8.81 A ATOM 1076 OD2 ASP A 275 36.623 26.680 177.346 1.00 8.43 A ATOM 1077 C ASP A 275 35.866 28.002 181.234 1.00 7.00 A ATOM 1078 O ASP A 275 36.957 28.240 180.693 1.00 7.47 A ATOM 1079 N ILE A 276 35.634 28.252 182.529 1.00 6.51 A ATOM 1080 CA ILE A 276 36.699 28.744 183.421 1.00 6.60 A ATOM 1081 CB ILE A 276 36.190 29.097 184.868 1.00 7.25 A ATOM 1082 CG2 ILE A 276 37.383 29.332 185.831 1.00 7.34 A ATOM 1083 CG1 ILE A 276 35.267 30.326 184.871 1.00 9.05 A ATOM 1084 CD1 ILE A 276 35.970 31.697 184.676 1.00 12.14 A ATOM 1085 C ILE A 276 37.759 27.650 183.522 1.00 8.47 A ATOM 1086 O ILE A 276 37.451 26.495 183.833 1.00 8.65 A ATOM 1087 N LYS A 277 38.976 28.025 183.142 1.00 7.22 A ATOM 1088 CA LYS A 277 40.139 27.152 183.179 1.00 6.80 A ATOM 1089 CB LYS A 277 40.106 26.077 182.078 1.00 8.00 A ATOM 1090 CG LYS A 277 40.140 26.534 180.648 1.00 6.57 A ATOM 1091 CD LYS A 277 40.157 25.310 179.770 1.00 9.85 A ATOM 1092 CE LYS A 277 40.085 25.671 178.319 1.00 10.08 A ATOM 1093 NZ LYS A 277 39.993 24.460 177.450 1.00 12.92 A ATOM 1094 C LYS A 277 41.406 27.968 183.104 1.00 7.80 A ATOM 1095 O LYS A 277 41.392 29.091 182.603 1.00 9.59 A ATOM 1096 N LEU A 278 42.507 27.392 183.583 1.00 9.89 A ATOM 1097 CA LEU A 278 43.797 28.078 183.591 1.00 8.36 A ATOM 1098 CB LEU A 278 44.840 27.221 184.295 1.00 8.17 A ATOM 1099 CG LEU A 278 44.707 26.894 185.782 1.00 8.04 A ATOM 1100 CD1 LEU A 278 45.802 25.911 186.112 1.00 8.41 A ATOM 1101 CD2 LEU A 278 44.818 28.136 186.659 1.00 10.25 A ATOM 1102 C LEU A 278 44.309 28.515 182.212 1.00 8.63 A ATOM 1103 O LEU A 278 45.001 29.522 182.108 1.00 9.02 A ATOM 1104 N GLU A 279 43.920 27.785 181.162 1.00 8.79 A ATOM 1105 CA GLU A 279 44.316 28.109 179.784 1.00 8.25 A ATOM 1106 CB GLU A 279 44.097 26.910 178.844 1.00 9.40 A ATOM 1107 CG GLU A 279 45.007 25.704 179.102 1.00 12.77 A ATOM 1108 CD GLU A 279 44.418 24.672 180.057 1.00 13.04 A ATOM 1109 OE1 GLU A 279 43.599 25.029 180.934 1.00 13.44 A ATOM 1110 OE2 GLU A 279 44.791 23.486 179.934 1.00 13.66 A ATOM 1111 C GLU A 279 43.570 29.326 179.232 1.00 8.31 A ATOM 1112 O GLU A 279 44.039 29.970 178.286 1.00 8.54 A ATOM 1113 N ASN A 280 42.419 29.632 179.836 1.00 6.31 A ATOM 1114 CA ASN A 280 41.575 30.767 179.440 1.00 7.33 A ATOM 1115 CB ASN A 280 40.096 30.368 179.453 1.00 6.01 A ATOM 1116 CG ASN A 280 39.725 29.456 178.304 1.00 8.77 A ATOM 1117 OD1 ASN A 280 40.528 29.223 177.402 1.00 8.00 A ATOM 1118 ND2 ASN A 280 38.495 28.942 178.325 1.00 7.13 A ATOM 1119 C ASN A 280 41.755 32.013 180.303 1.00 6.80 A ATOM 1120 O ASN A 280 41.158 33.056 180.024 1.00 10.46 A ATOM 1121 N LEU A 281 42.545 31.886 181.370 1.00 7.47 A ATOM 1122 CA LEU A 281 42.817 32.998 182.287 1.00 8.41 A ATOM 1123 CB LEU A 281 42.674 32.534 183.744 1.00 8.16 A ATOM 1124 CG LEU A 281 41.296 31.986 184.143 1.00 8.45 A ATOM 1125 CD1 LEU A 281 41.389 31.184 185.432 1.00 9.90 A ATOM 1126 CD2 LEU A 281 40.265 33.095 184.246 1.00 11.76 A ATOM 1127 C LEU A 281 44.222 33.526 182.001 1.00 9.46 A ATOM 1128 O LEU A 281 45.219 32.868 182.292 1.00 10.14 A ATOM 1129 N MET A 282 44.281 34.707 181.392 1.00 9.92 A ATOM 1130 CA MET A 282 45.548 35.332 181.010 1.00 9.92 A ATOM 1131 CB MET A 282 45.442 35.936 179.604 1.00 9.90 A ATOM 1132 CG MET A 282 44.780 35.093 178.531 1.00 13.02 A ATOM 1133 SD MET A 282 45.649 33.583 178.146 1.00 15.90 A ATOM 1134 CE MET A 282 47.048 34.238 177.267 1.00 13.84 A ATOM 1135 C MET A 282 45.971 36.464 181.930 1.00 10.24 A ATOM 1136 O MET A 282 45.190 36.940 182.745 1.00 11.10 A ATOM 1137 N LEU A 283 47.224 36.889 181.777 1.00 9.57 A ATOM 1138 CA LEU A 283 47.762 38.018 182.530 1.00 9.80 A ATOM 1139 CB LEU A 283 48.981 37.617 183.376 1.00 11.37 A ATOM 1140 CG LEU A 283 48.810 36.691 184.587 1.00 11.11 A ATOM 1141 CD1 LEU A 283 50.123 36.609 185.358 1.00 12.01 A ATOM 1142 CD2 LEU A 283 47.711 37.212 185.497 1.00 12.37 A ATOM 1143 C LEU A 283 48.171 39.075 181.515 1.00 10.80 A ATOM 1144 O LEU A 283 48.740 38.735 180.475 1.00 10.89 A ATOM 1145 N ASP A 284 47.818 40.338 181.767 1.00 12.21 A ATOM 1146 CA ASP A 284 48.218 41.426 180.862 1.00 12.15 A ATOM 1147 CB ASP A 284 47.216 42.610 180.872 1.00 12.94 A ATOM 1148 CG ASP A 284 47.055 43.295 182.242 1.00 15.18 A ATOM 1149 OD1 ASP A 284 47.848 43.064 183.177 1.00 12.85 A ATOM 1150 OD2 ASP A 284 46.106 44.099 182.371 1.00 15.48 A ATOM 1151 C ASP A 284 49.651 41.858 181.209 1.00 13.96 A ATOM 1152 O ASP A 284 50.250 41.285 182.123 1.00 12.43 A ATOM 1153 N LYS A 285 50.174 42.880 180.525 1.00 15.26 A ATOM 1154 CA LYS A 285 51.541 43.372 180.764 1.00 18.56 A ATOM 1155 CB LYS A 285 51.929 44.434 179.721 1.00 21.83 A ATOM 1156 CG LYS A 285 50.982 45.626 179.604 1.00 26.06 A ATOM 1157 CD LYS A 285 51.481 46.619 178.557 1.00 29.53 A ATOM 1158 CE LYS A 285 50.449 47.704 178.275 1.00 31.29 A ATOM 1159 NZ LYS A 285 49.206 47.152 177.657 1.00 33.75 A ATOM 1160 C LYS A 285 51.828 43.890 182.181 1.00 16.68 A ATOM 1161 O LYS A 285 52.987 43.955 182.595 1.00 18.17 A ATOM 1162 N ASP A 286 50.765 44.209 182.919 1.00 16.70 A ATOM 1163 CA ASP A 286 50.872 44.718 184.290 1.00 15.22 A ATOM 1164 CB ASP A 286 49.838 45.829 184.529 1.00 15.56 A ATOM 1165 CG ASP A 286 50.035 47.032 183.613 1.00 19.79 A ATOM 1166 OD1 ASP A 286 51.161 47.570 183.547 1.00 21.62 A ATOM 1167 OD2 ASP A 286 49.055 47.444 182.957 1.00 22.25 A ATOM 1168 C ASP A 286 50.715 43.626 185.356 1.00 14.92 A ATOM 1169 O ASP A 286 51.060 43.842 186.521 1.00 16.19 A ATOM 1170 N GLY A 287 50.191 42.466 184.957 1.00 13.57 A ATOM 1171 CA GLY A 287 49.999 41.359 185.887 1.00 11.70 A ATOM 1172 C GLY A 287 48.574 41.120 186.350 1.00 11.64 A ATOM 1173 O GLY A 287 48.339 40.316 187.258 1.00 11.78 A ATOM 1174 N HIS A 288 47.629 41.834 185.743 1.00 9.91 A ATOM 1175 CA HIS A 288 46.207 41.697 186.066 1.00 11.23 A ATOM 1176 CB HIS A 288 45.471 43.017 185.834 1.00 13.28 A ATOM 1177 CG HIS A 288 45.808 44.088 186.822 1.00 14.63 A ATOM 1178 CD2 HIS A 288 46.526 45.228 186.691 1.00 16.43 A ATOM 1179 ND1 HIS A 288 45.356 44.068 188.123 1.00 15.31 A ATOM 1180 CE1 HIS A 288 45.779 45.150 188.752 1.00 16.81 A ATOM 1181 NE2 HIS A 288 46.492 45.871 187.904 1.00 17.87 A ATOM 1182 C HIS A 288 45.576 40.628 185.179 1.00 10.60 A ATOM 1183 O HIS A 288 46.028 40.410 184.055 1.00 11.22 A ATOM 1184 N ILE A 289 44.519 39.991 185.686 1.00 10.82 A ATOM 1185 CA ILE A 289 43.774 38.947 184.971 1.00 10.21 A ATOM 1186 CB ILE A 289 42.739 38.227 185.933 1.00 9.51 A ATOM 1187 CG2 ILE A 289 41.618 37.445 185.165 1.00 7.93 A ATOM 1188 CG1 ILE A 289 43.473 37.322 186.929 1.00 11.18 A ATOM 1189 CD1 ILE A 289 44.069 36.033 186.354 1.00 13.48 A ATOM 1190 C ILE A 289 43.032 39.488 183.748 1.00 10.59 A ATOM 1191 O ILE A 289 42.554 40.621 183.746 1.00 11.51 A ATOM 1192 N LYS A 290 43.036 38.685 182.688 1.00 11.77 A ATOM 1193 CA LYS A 290 42.324 38.979 181.455 1.00 11.00 A ATOM 1194 CB LYS A 290 43.252 39.492 180.341 1.00 13.10 A ATOM 1195 CG LYS A 290 43.686 40.953 180.447 1.00 14.99 A ATOM 1196 CD LYS A 290 42.529 41.930 180.290 1.00 18.52 A ATOM 1197 CE LYS A 290 43.034 43.364 180.295 1.00 22.11 A ATOM 1198 NZ LYS A 290 41.922 44.337 180.126 1.00 26.55 A ATOM 1199 C LYS A 290 41.695 37.664 181.035 1.00 11.30 A ATOM 1200 O LYS A 290 42.397 36.735 180.631 1.00 12.04 A ATOM 1201 N ILE A 291 40.385 37.542 181.229 1.00 9.93 A ATOM 1202 CA ILE A 291 39.682 36.332 180.811 1.00 9.56 A ATOM 1203 CB ILE A 291 38.279 36.183 181.477 1.00 10.13 A ATOM 1204 CG2 ILE A 291 37.582 34.918 180.959 1.00 10.54 A ATOM 1205 CG1 ILE A 291 38.399 36.142 183.006 1.00 11.61 A ATOM 1206 CD1 ILE A 291 37.094 35.832 183.747 1.00 12.24 A ATOM 1207 C ILE A 291 39.510 36.439 179.294 1.00 9.16 A ATOM 1208 O ILE A 291 39.099 37.482 178.788 1.00 10.60 A ATOM 1209 N THR A 292 39.902 35.382 178.590 1.00 8.25 A ATOM 1210 CA THR A 292 39.777 35.311 177.142 1.00 9.83 A ATOM 1211 CB THR A 292 41.179 35.209 176.452 1.00 11.15 A ATOM 1212 OG1 THR A 292 41.037 35.449 175.048 1.00 12.68 A ATOM 1213 CG2 THR A 292 41.833 33.831 176.672 1.00 10.76 A ATOM 1214 C THR A 292 38.899 34.098 176.828 1.00 9.68 A ATOM 1215 O THR A 292 38.379 33.467 177.753 1.00 10.43 A ATOM 1216 N ASP A 293 38.721 33.799 175.537 1.00 9.17 A ATOM 1217 CA ASP A 293 37.931 32.655 175.053 1.00 10.04 A ATOM 1218 CB ASP A 293 38.658 31.336 175.377 1.00 9.36 A ATOM 1219 CG ASP A 293 37.989 30.109 174.770 1.00 10.66 A ATOM 1220 OD1 ASP A 293 37.099 30.252 173.899 1.00 10.21 A ATOM 1221 OD2 ASP A 293 38.361 28.988 175.171 1.00 10.02 A ATOM 1222 C ASP A 293 36.473 32.625 175.536 1.00 9.58 A ATOM 1223 O ASP A 293 36.118 31.901 176.475 1.00 10.78 A ATOM 1224 N PHE A 294 35.634 33.371 174.833 1.00 9.42 A ATOM 1225 CA PHE A 294 34.216 33.457 175.151 1.00 10.65 A ATOM 1226 CB PHE A 294 33.765 34.919 175.027 1.00 8.98 A ATOM 1227 CG PHE A 294 34.492 35.850 175.965 1.00 10.40 A ATOM 1228 CD1 PHE A 294 35.657 36.524 175.545 1.00 10.44 A ATOM 1229 CD2 PHE A 294 34.037 36.034 177.284 1.00 10.22 A ATOM 1230 CE1 PHE A 294 36.372 37.377 176.429 1.00 10.90 A ATOM 1231 CE2 PHE A 294 34.734 36.880 178.186 1.00 10.17 A ATOM 1232 CZ PHE A 294 35.912 37.556 177.753 1.00 9.39 A ATOM 1233 C PHE A 294 33.401 32.528 174.243 1.00 10.59 A ATOM 1234 O PHE A 294 32.197 32.718 174.062 1.00 11.98 A ATOM 1235 N GLY A 295 34.074 31.490 173.735 1.00 9.82 A ATOM 1236 CA GLY A 295 33.481 30.518 172.823 1.00 10.01 A ATOM 1237 C GLY A 295 32.307 29.675 173.272 1.00 11.65 A ATOM 1238 O GLY A 295 31.543 29.186 172.434 1.00 12.48 A ATOM 1239 N LEU A 296 32.188 29.469 174.582 1.00 10.57 A ATOM 1240 CA LEU A 296 31.105 28.666 175.139 1.00 11.63 A ATOM 1241 CB LEU A 296 31.663 27.439 175.874 1.00 10.26 A ATOM 1242 CG LEU A 296 32.185 26.311 174.973 1.00 13.35 A ATOM 1243 CD1 LEU A 296 32.808 25.234 175.818 1.00 11.29 A ATOM 1244 CD2 LEU A 296 31.069 25.737 174.094 1.00 12.10 A ATOM 1245 C LEU A 296 30.147 29.452 176.022 1.00 10.80 A ATOM 1246 O LEU A 296 29.403 28.874 176.817 1.00 12.17 A ATOM 1247 N CYS A 297 30.139 30.773 175.845 1.00 10.80 A ATOM 1248 CA CYS A 297 29.254 31.652 176.603 1.00 13.22 A ATOM 1249 CB CYS A 297 29.650 33.120 176.428 1.00 13.44 A ATOM 1250 SG CYS A 297 31.066 33.657 177.396 1.00 13.71 A ATOM 1251 C CYS A 297 27.807 31.491 176.152 1.00 14.72 A ATOM 1252 O CYS A 297 27.541 31.040 175.037 1.00 15.60 A ATOM 1253 N LYS A 298 26.883 31.807 177.053 1.00 14.15 A ATOM 1254 CA LYS A 298 25.461 31.753 176.750 1.00 13.85 A ATOM 1255 CB LYS A 298 24.778 30.562 177.435 1.00 15.15 A ATOM 1256 CG LYS A 298 23.365 30.255 176.908 1.00 15.78 A ATOM 1257 CD LYS A 298 23.368 29.620 175.525 1.00 16.76 A ATOM 1258 CE LYS A 298 21.948 29.414 175.021 1.00 17.84 A ATOM 1259 NZ LYS A 298 21.915 28.831 173.647 1.00 19.96 A ATOM 1260 C LYS A 298 24.862 33.058 177.241 1.00 14.64 A ATOM 1261 O LYS A 298 25.089 33.463 178.386 1.00 11.66 A ATOM 1262 N GLU A 299 24.146 33.733 176.343 1.00 14.33 A ATOM 1263 CA GLU A 299 23.482 35.003 176.637 1.00 16.11 A ATOM 1264 CB GLU A 299 23.466 35.897 175.395 1.00 17.68 A ATOM 1265 CG GLU A 299 24.812 36.408 174.942 1.00 19.12 A ATOM 1266 CD GLU A 299 24.710 37.162 173.631 1.00 21.04 A ATOM 1267 OE1 GLU A 299 24.554 38.400 173.663 1.00 24.87 A ATOM 1268 OE2 GLU A 299 24.763 36.510 172.569 1.00 22.96 A ATOM 1269 C GLU A 299 22.039 34.780 177.075 1.00 15.92 A ATOM 1270 O GLU A 299 21.492 33.688 176.902 1.00 14.96 A ATOM 1271 N GLY A 300 21.446 35.826 177.653 1.00 15.75 A ATOM 1272 CA GLY A 300 20.060 35.794 178.099 1.00 17.47 A ATOM 1273 C GLY A 300 19.732 34.960 179.322 1.00 17.70 A ATOM 1274 O GLY A 300 18.566 34.623 179.545 1.00 20.16 A ATOM 1275 N ILE A 301 20.755 34.633 180.114 1.00 17.12 A ATOM 1276 CA ILE A 301 20.582 33.826 181.321 1.00 17.87 A ATOM 1277 CB ILE A 301 21.690 32.723 181.437 1.00 16.61 A ATOM 1278 CG2 ILE A 301 21.438 31.802 182.641 1.00 17.26 A ATOM 1279 CG1 ILE A 301 21.796 31.902 180.138 1.00 16.71 A ATOM 1280 CD1 ILE A 301 20.506 31.195 179.667 1.00 15.02 A ATOM 1281 C ILE A 301 20.545 34.713 182.571 1.00 18.46 A ATOM 1282 O ILE A 301 21.584 35.030 183.164 1.00 17.14 A ATOM 1283 N SER A 302 19.332 35.132 182.928 1.00 20.13 A ATOM 1284 CA SER A 302 19.077 35.983 184.090 1.00 22.53 A ATOM 1285 CB SER A 302 18.073 37.083 183.727 1.00 23.18 A ATOM 1286 OG SER A 302 16.908 36.542 183.122 1.00 25.28 A ATOM 1287 C SER A 302 18.524 35.159 185.245 1.00 23.86 A ATOM 1288 O SER A 302 17.776 34.208 185.020 1.00 23.97 A ATOM 1289 N ASP A 303 18.886 35.547 186.472 1.00 26.08 A ATOM 1290 CA ASP A 303 18.456 34.896 187.721 1.00 27.31 A ATOM 1291 CB ASP A 303 17.005 35.281 188.076 1.00 30.01 A ATOM 1292 CG ASP A 303 16.838 36.766 188.352 1.00 32.98 A ATOM 1293 OD1 ASP A 303 16.891 37.163 189.536 1.00 34.13 A ATOM 1294 OD2 ASP A 303 16.644 37.534 187.385 1.00 36.20 A ATOM 1295 C ASP A 303 18.652 33.370 187.737 1.00 26.42 A ATOM 1296 O ASP A 303 19.787 32.892 187.664 1.00 27.68 A ATOM 1297 N GLY A 304 17.544 32.628 187.755 1.00 24.67 A ATOM 1298 CA GLY A 304 17.595 31.177 187.772 1.00 22.31 A ATOM 1299 C GLY A 304 17.347 30.513 186.429 1.00 21.41 A ATOM 1300 O GLY A 304 16.949 29.346 186.398 1.00 22.36 A ATOM 1301 N ALA A 305 17.588 31.234 185.326 1.00 19.38 A ATOM 1302 CA ALA A 305 17.400 30.692 183.974 1.00 16.23 A ATOM 1303 CB ALA A 305 17.534 31.784 182.923 1.00 18.12 A ATOM 1304 C ALA A 305 18.412 29.576 183.723 1.00 15.49 A ATOM 1305 O ALA A 305 19.523 29.604 184.259 1.00 16.41 A ATOM 1306 N THR A 306 18.008 28.582 182.939 1.00 14.64 A ATOM 1307 CA THR A 306 18.857 27.423 182.679 1.00 14.69 A ATOM 1308 CB THR A 306 18.147 26.135 183.143 1.00 14.73 A ATOM 1309 OG1 THR A 306 16.953 25.939 182.373 1.00 14.38 A ATOM 1310 CG2 THR A 306 17.801 26.183 184.639 1.00 15.77 A ATOM 1311 C THR A 306 19.374 27.222 181.249 1.00 13.86 A ATOM 1312 O THR A 306 18.902 27.858 180.305 1.00 13.55 A ATOM 1313 N MET A 307 20.379 26.348 181.126 1.00 12.76 A ATOM 1314 CA MET A 307 21.030 25.989 179.858 1.00 13.15 A ATOM 1315 CB MET A 307 22.487 26.452 179.848 1.00 14.43 A ATOM 1316 CG MET A 307 22.665 27.950 179.895 1.00 17.96 A ATOM 1317 SD MET A 307 24.155 28.447 180.732 1.00 15.06 A ATOM 1318 CE MET A 307 23.609 28.298 182.407 1.00 16.64 A ATOM 1319 C MET A 307 20.997 24.475 179.689 1.00 14.21 A ATOM 1320 O MET A 307 21.014 23.740 180.679 1.00 13.98 A ATOM 1321 N LYS A 308 21.002 24.012 178.438 1.00 13.94 A ATOM 1322 CA LYS A 308 20.933 22.579 178.138 1.00 16.40 A ATOM 1323 CB LYS A 308 19.650 22.275 177.345 1.00 20.02 A ATOM 1324 CG LYS A 308 18.356 22.428 178.138 1.00 26.06 A ATOM 1325 CD LYS A 308 17.131 22.272 177.254 1.00 29.32 A ATOM 1326 CE LYS A 308 15.855 22.516 178.049 1.00 31.48 A ATOM 1327 NZ LYS A 308 14.645 22.478 177.180 1.00 34.34 A ATOM 1328 C LYS A 308 22.121 21.939 177.414 1.00 14.91 A ATOM 1329 O LYS A 308 22.251 20.714 177.428 1.00 15.41 A ATOM 1330 N PTH A 309 22.995 22.753 176.816 1.00 14.40 A ATOM 1331 CA PTH A 309 24.145 22.248 176.051 1.00 12.21 A ATOM 1332 CB PTH A 309 24.836 23.392 175.261 1.00 13.59 A ATOM 1333 OG1 PTH A 309 23.864 24.142 174.505 1.00 13.57 A ATOM 1334 CG2 PTH A 309 25.863 22.833 174.267 1.00 11.34 A ATOM 1335 C PTH A 309 25.200 21.515 176.902 1.00 13.43 A ATOM 1336 O PTH A 309 25.651 22.046 177.914 1.00 12.16 A ATOM 1337 P PTH A 309 23.695 25.504 174.704 1.00 15.40 A ATOM 1338 O1P PTH A 309 24.865 26.333 174.283 1.00 15.17 A ATOM 1339 O2P PTH A 309 23.252 25.585 176.140 1.00 15.51 A ATOM 1340 O3P PTH A 309 22.569 25.829 173.656 1.00 15.33 A ATOM 1341 N PHE A 310 25.565 20.297 176.498 1.00 11.60 A ATOM 1342 CA PHE A 310 26.607 19.533 177.193 1.00 11.72 A ATOM 1343 CB PHE A 310 26.439 18.021 176.927 1.00 12.18 A ATOM 1344 CG PHE A 310 27.425 17.127 177.668 1.00 11.43 A ATOM 1345 CD1 PHE A 310 27.917 15.962 177.046 1.00 14.94 A ATOM 1346 CD2 PHE A 310 27.840 17.415 178.992 1.00 11.04 A ATOM 1347 CE1 PHE A 310 28.810 15.083 177.728 1.00 13.98 A ATOM 1348 CE2 PHE A 310 28.729 16.553 179.688 1.00 11.48 A ATOM 1349 CZ PHE A 310 29.216 15.379 179.053 1.00 13.60 A ATOM 1350 C PHE A 310 27.919 20.069 176.600 1.00 11.28 A ATOM 1351 O PHE A 310 28.305 19.708 175.484 1.00 11.72 A ATOM 1352 N CYS A 311 28.550 20.983 177.338 1.00 10.71 A ATOM 1353 CA CYS A 311 29.790 21.617 176.905 1.00 11.00 A ATOM 1354 CB CYS A 311 29.476 22.836 176.030 1.00 11.91 A ATOM 1355 SG CYS A 311 28.629 24.175 176.875 1.00 12.31 A ATOM 1356 C CYS A 311 30.689 22.042 178.063 1.00 10.60 A ATOM 1357 O CYS A 311 30.269 22.039 179.220 1.00 8.91 A ATOM 1358 N GLY A 312 31.911 22.447 177.719 1.00 11.10 A ATOM 1359 CA GLY A 312 32.893 22.878 178.705 1.00 11.36 A ATOM 1360 C GLY A 312 34.201 22.154 178.454 1.00 10.56 A ATOM 1361 O GLY A 312 34.472 21.741 177.329 1.00 11.29 A ATOM 1362 N THR A 313 35.017 22.018 179.495 1.00 9.91 A ATOM 1363 CA THR A 313 36.294 21.314 179.420 1.00 9.63 A ATOM 1364 CB THR A 313 37.469 22.273 179.754 1.00 8.21 A ATOM 1365 OG1 THR A 313 37.591 23.245 178.710 1.00 8.40 A ATOM 1366 CG2 THR A 313 38.767 21.538 179.842 1.00 9.49 A ATOM 1367 C THR A 313 36.150 20.163 180.427 1.00 10.10 A ATOM 1368 O THR A 313 35.793 20.414 181.583 1.00 9.15 A ATOM 1369 N PRO A 314 36.419 18.897 180.003 1.00 10.35 A ATOM 1370 CD PRO A 314 36.972 18.514 178.683 1.00 12.20 A ATOM 1371 CA PRO A 314 36.309 17.692 180.842 1.00 10.55 A ATOM 1372 CB PRO A 314 37.131 16.667 180.064 1.00 11.31 A ATOM 1373 CG PRO A 314 36.807 17.012 178.677 1.00 11.44 A ATOM 1374 C PRO A 314 36.693 17.750 182.321 1.00 9.90 A ATOM 1375 O PRO A 314 35.857 17.489 183.190 1.00 10.46 A ATOM 1376 N GLU A 315 37.925 18.169 182.595 1.00 10.50 A ATOM 1377 CA GLU A 315 38.462 18.264 183.956 1.00 9.77 A ATOM 1378 CB GLU A 315 39.981 18.492 183.890 1.00 11.68 A ATOM 1379 CG GLU A 315 40.800 17.322 183.303 1.00 12.07 A ATOM 1380 CD GLU A 315 40.854 17.269 181.773 1.00 15.42 A ATOM 1381 OE1 GLU A 315 40.240 18.114 181.084 1.00 14.43 A ATOM 1382 OE2 GLU A 315 41.543 16.370 181.250 1.00 18.17 A ATOM 1383 C GLU A 315 37.821 19.352 184.820 1.00 9.08 A ATOM 1384 O GLU A 315 37.923 19.310 186.049 1.00 10.42 A ATOM 1385 N TYR A 316 37.125 20.284 184.167 1.00 7.79 A ATOM 1386 CA TYR A 316 36.479 21.420 184.824 1.00 8.92 A ATOM 1387 CB TYR A 316 36.898 22.718 184.127 1.00 9.19 A ATOM 1388 CG TYR A 316 38.344 23.088 184.339 1.00 8.52 A ATOM 1389 CD1 TYR A 316 39.367 22.514 183.555 1.00 9.47 A ATOM 1390 CE1 TYR A 316 40.724 22.849 183.762 1.00 9.76 A ATOM 1391 CD2 TYR A 316 38.706 24.005 185.337 1.00 10.20 A ATOM 1392 CE2 TYR A 316 40.062 24.348 185.560 1.00 8.85 A ATOM 1393 CZ TYR A 316 41.059 23.775 184.765 1.00 9.50 A ATOM 1394 OH TYR A 316 42.351 24.203 184.909 1.00 12.63 A ATOM 1395 C TYR A 316 34.958 21.371 184.902 1.00 9.80 A ATOM 1396 O TYR A 316 34.339 22.274 185.477 1.00 10.39 A ATOM 1397 N LEU A 317 34.359 20.325 184.331 1.00 8.92 A ATOM 1398 CA LEU A 317 32.905 20.175 184.327 1.00 9.94 A ATOM 1399 CB LEU A 317 32.477 18.977 183.478 1.00 9.39 A ATOM 1400 CG LEU A 317 32.619 19.044 181.963 1.00 10.78 A ATOM 1401 CD1 LEU A 317 32.104 17.748 181.394 1.00 11.21 A ATOM 1402 CD2 LEU A 317 31.866 20.222 181.373 1.00 9.97 A ATOM 1403 C LEU A 317 32.284 20.030 185.704 1.00 8.12 A ATOM 1404 O LEU A 317 32.814 19.324 186.564 1.00 8.69 A ATOM 1405 N ALA A 318 31.175 20.740 185.903 1.00 10.04 A ATOM 1406 CA ALA A 318 30.412 20.701 187.148 1.00 9.46 A ATOM 1407 CB ALA A 318 29.508 21.928 187.236 1.00 10.35 A ATOM 1408 C ALA A 318 29.595 19.405 187.170 1.00 8.52 A ATOM 1409 O ALA A 318 29.194 18.929 186.107 1.00 9.09 A ATOM 1410 N PRO A 319 29.366 18.797 188.365 1.00 9.01 A ATOM 1411 CD PRO A 319 29.815 19.202 189.707 1.00 10.61 A ATOM 1412 CA PRO A 319 28.594 17.548 188.466 1.00 8.90 A ATOM 1413 CB PRO A 319 28.510 17.315 189.973 1.00 9.23 A ATOM 1414 CG PRO A 319 29.769 17.906 190.466 1.00 10.30 A ATOM 1415 C PRO A 319 27.208 17.605 187.844 1.00 8.12 A ATOM 1416 O PRO A 319 26.760 16.625 187.253 1.00 10.13 A ATOM 1417 N GLU A 320 26.556 18.767 187.941 1.00 9.41 A ATOM 1418 CA GLU A 320 25.215 18.952 187.372 1.00 9.08 A ATOM 1419 CB GLU A 320 24.556 20.240 187.895 1.00 10.40 A ATOM 1420 CG GLU A 320 25.240 21.552 187.504 1.00 10.56 A ATOM 1421 CD GLU A 320 26.171 22.108 188.563 1.00 11.83 A ATOM 1422 OE1 GLU A 320 26.765 21.329 189.337 1.00 10.20 A ATOM 1423 OE2 GLU A 320 26.326 23.348 188.600 1.00 10.61 A ATOM 1424 C GLU A 320 25.197 18.896 185.837 1.00 10.94 A ATOM 1425 O GLU A 320 24.207 18.464 185.245 1.00 10.55 A ATOM 1426 N VAL A 321 26.311 19.288 185.209 1.00 9.07 A ATOM 1427 CA VAL A 321 26.454 19.255 183.744 1.00 10.14 A ATOM 1428 CB VAL A 321 27.662 20.132 183.255 1.00 8.06 A ATOM 1429 CG1 VAL A 321 27.740 20.181 181.718 1.00 10.09 A ATOM 1430 CG2 VAL A 321 27.528 21.545 183.784 1.00 9.95 A ATOM 1431 C VAL A 321 26.639 17.789 183.313 1.00 10.09 A ATOM 1432 O VAL A 321 26.296 17.414 182.190 1.00 10.46 A ATOM 1433 N LEU A 322 27.136 16.964 184.238 1.00 10.76 A ATOM 1434 CA LEU A 322 27.346 15.534 183.999 1.00 10.24 A ATOM 1435 CB LEU A 322 28.532 15.021 184.815 1.00 10.24 A ATOM 1436 CG LEU A 322 29.875 15.467 184.246 1.00 11.13 A ATOM 1437 CD1 LEU A 322 30.975 15.144 185.229 1.00 10.25 A ATOM 1438 CD2 LEU A 322 30.106 14.781 182.906 1.00 10.66 A ATOM 1439 C LEU A 322 26.093 14.703 184.261 1.00 9.62 A ATOM 1440 O LEU A 322 26.117 13.466 184.215 1.00 9.76 A ATOM 1441 N GLU A 323 25.003 15.411 184.536 1.00 11.36 A ATOM 1442 CA GLU A 323 23.695 14.819 184.765 1.00 12.36 A ATOM 1443 CB GLU A 323 23.092 15.307 186.086 1.00 12.59 A ATOM 1444 CG GLU A 323 23.833 14.842 187.337 1.00 12.32 A ATOM 1445 CD GLU A 323 23.263 15.415 188.628 1.00 14.18 A ATOM 1446 OE1 GLU A 323 22.733 16.546 188.612 1.00 13.47 A ATOM 1447 OE2 GLU A 323 23.353 14.733 189.671 1.00 14.44 A ATOM 1448 C GLU A 323 22.811 15.244 183.596 1.00 14.58 A ATOM 1449 O GLU A 323 23.160 16.174 182.864 1.00 15.03 A ATOM 1450 N ASP A 324 21.690 14.549 183.399 1.00 15.81 A ATOM 1451 CA ASP A 324 20.753 14.878 182.322 1.00 18.79 A ATOM 1452 CB ASP A 324 19.741 13.747 182.104 1.00 20.75 A ATOM 1453 CG ASP A 324 20.371 12.482 181.558 1.00 23.45 A ATOM 1454 OD1 ASP A 324 21.223 12.558 180.644 1.00 24.22 A ATOM 1455 OD2 ASP A 324 19.981 11.399 182.032 1.00 24.40 A ATOM 1456 C ASP A 324 19.992 16.175 182.608 1.00 19.31 A ATOM 1457 O ASP A 324 20.058 16.716 183.715 1.00 18.94 A ATOM 1458 N ASN A 325 19.278 16.653 181.587 1.00 22.17 A ATOM 1459 CA ASN A 325 18.462 17.874 181.618 1.00 23.16 A ATOM 1460 CB ASN A 325 17.340 17.785 182.688 1.00 26.60 A ATOM 1461 CG ASN A 325 16.054 18.515 182.278 1.00 29.66 A ATOM 1462 OD1 ASN A 325 15.296 18.973 183.133 1.00 31.41 A ATOM 1463 ND2 ASN A 325 15.802 18.610 180.973 1.00 33.05 A ATOM 1464 C ASN A 325 19.261 19.189 181.691 1.00 23.60 A ATOM 1465 O ASN A 325 20.353 19.283 181.119 1.00 25.24 A ATOM 1466 N ASP A 326 18.748 20.167 182.434 1.00 20.49 A ATOM 1467 CA ASP A 326 19.349 21.496 182.516 1.00 17.99 A ATOM 1468 CB ASP A 326 18.260 22.535 182.202 1.00 18.89 A ATOM 1469 CG ASP A 326 17.047 22.458 183.142 1.00 23.31 A ATOM 1470 OD1 ASP A 326 17.079 21.724 184.155 1.00 26.82 A ATOM 1471 OD2 ASP A 326 16.055 23.172 182.868 1.00 25.35 A ATOM 1472 C ASP A 326 20.168 21.916 183.744 1.00 16.92 A ATOM 1473 O ASP A 326 20.117 21.271 184.787 1.00 16.41 A ATOM 1474 N TYR A 327 20.902 23.023 183.602 1.00 14.26 A ATOM 1475 CA TYR A 327 21.745 23.568 184.673 1.00 12.93 A ATOM 1476 CB TYR A 327 23.176 22.999 184.580 1.00 10.53 A ATOM 1477 CG TYR A 327 23.885 23.243 183.259 1.00 9.84 A ATOM 1478 CD1 TYR A 327 24.635 24.423 183.043 1.00 9.94 A ATOM 1479 CE1 TYR A 327 25.262 24.679 181.809 1.00 9.67 A ATOM 1480 CD2 TYR A 327 23.784 22.315 182.198 1.00 9.05 A ATOM 1481 CE2 TYR A 327 24.407 22.562 180.953 1.00 8.79 A ATOM 1482 CZ TYR A 327 25.141 23.752 180.771 1.00 9.34 A ATOM 1483 OH TYR A 327 25.713 24.039 179.558 1.00 11.63 A ATOM 1484 C TYR A 327 21.765 25.100 184.689 1.00 11.84 A ATOM 1485 O TYR A 327 21.590 25.735 183.646 1.00 13.50 A ATOM 1486 N GLY A 328 22.049 25.671 185.860 1.00 13.42 A ATOM 1487 CA GLY A 328 22.086 27.117 186.028 1.00 12.25 A ATOM 1488 C GLY A 328 23.457 27.768 185.989 1.00 10.86 A ATOM 1489 O GLY A 328 24.462 27.117 185.671 1.00 12.06 A ATOM 1490 N ARG A 329 23.492 29.060 186.325 1.00 10.44 A ATOM 1491 CA ARG A 329 24.719 29.872 186.321 1.00 11.12 A ATOM 1492 CB ARG A 329 24.385 31.369 186.466 1.00 13.08 A ATOM 1493 CG ARG A 329 23.730 31.787 187.773 1.00 13.12 A ATOM 1494 CD ARG A 329 23.319 33.241 187.706 1.00 17.93 A ATOM 1495 NE ARG A 329 22.595 33.662 188.903 1.00 22.88 A ATOM 1496 CZ ARG A 329 22.070 34.873 189.082 1.00 25.02 A ATOM 1497 NH1 ARG A 329 22.180 35.806 188.143 1.00 27.77 A ATOM 1498 NH2 ARG A 329 21.426 35.150 190.207 1.00 27.77 A ATOM 1499 C ARG A 329 25.812 29.488 187.318 1.00 11.17 A ATOM 1500 O ARG A 329 26.962 29.906 187.158 1.00 9.66 A ATOM 1501 N ALA A 330 25.458 28.653 188.299 1.00 10.24 A ATOM 1502 CA ALA A 330 26.382 28.195 189.340 1.00 10.50 A ATOM 1503 CB ALA A 330 25.633 27.407 190.407 1.00 9.00 A ATOM 1504 C ALA A 330 27.575 27.383 188.831 1.00 8.85 A ATOM 1505 O ALA A 330 28.532 27.165 189.576 1.00 8.15 A ATOM 1506 N VAL A 331 27.525 26.967 187.561 1.00 8.42 A ATOM 1507 CA VAL A 331 28.614 26.202 186.939 1.00 8.41 A ATOM 1508 CB VAL A 331 28.253 25.700 185.510 1.00 9.21 A ATOM 1509 CG1 VAL A 331 27.118 24.714 185.601 1.00 9.28 A ATOM 1510 CG2 VAL A 331 27.874 26.864 184.575 1.00 12.35 A ATOM 1511 C VAL A 331 29.920 27.000 186.901 1.00 6.92 A ATOM 1512 O VAL A 331 31.002 26.426 186.998 1.00 7.72 A ATOM 1513 N ASP A 332 29.794 28.329 186.829 1.00 8.72 A ATOM 1514 CA ASP A 332 30.949 29.230 186.808 1.00 8.42 A ATOM 1515 CB ASP A 332 30.543 30.648 186.390 1.00 9.09 A ATOM 1516 CG ASP A 332 30.297 30.779 184.891 1.00 10.81 A ATOM 1517 OD1 ASP A 332 30.726 29.897 184.116 1.00 8.54 A ATOM 1518 OD2 ASP A 332 29.686 31.788 184.483 1.00 10.71 A ATOM 1519 C ASP A 332 31.663 29.279 188.156 1.00 8.16 A ATOM 1520 O ASP A 332 32.877 29.489 188.205 1.00 9.32 A ATOM 1521 N TRP A 333 30.914 29.049 189.240 1.00 7.97 A ATOM 1522 CA TRP A 333 31.499 29.055 190.582 1.00 7.70 A ATOM 1523 CB TRP A 333 30.460 29.418 191.655 1.00 7.03 A ATOM 1524 CG TRP A 333 29.794 30.749 191.372 1.00 8.05 A ATOM 1525 CD2 TRP A 333 30.429 32.035 191.199 1.00 9.02 A ATOM 1526 CE2 TRP A 333 29.413 32.950 190.820 1.00 9.48 A ATOM 1527 CE3 TRP A 333 31.759 32.506 191.320 1.00 8.07 A ATOM 1528 CD1 TRP A 333 28.470 30.948 191.117 1.00 8.00 A ATOM 1529 NE1 TRP A 333 28.232 32.257 190.782 1.00 10.50 A ATOM 1530 CZ2 TRP A 333 29.679 34.312 190.554 1.00 10.90 A ATOM 1531 CZ3 TRP A 333 32.028 33.870 191.058 1.00 10.17 A ATOM 1532 CH2 TRP A 333 30.985 34.753 190.678 1.00 10.71 A ATOM 1533 C TRP A 333 32.249 27.764 190.870 1.00 7.92 A ATOM 1534 O TRP A 333 33.278 27.782 191.556 1.00 9.29 A ATOM 1535 N TRP A 334 31.792 26.669 190.252 1.00 8.16 A ATOM 1536 CA TRP A 334 32.473 25.374 190.367 1.00 6.51 A ATOM 1537 CB TRP A 334 31.663 24.248 189.698 1.00 7.58 A ATOM 1538 CG TRP A 334 32.431 22.936 189.535 1.00 7.77 A ATOM 1539 CD2 TRP A 334 32.484 21.843 190.458 1.00 6.79 A ATOM 1540 CE2 TRP A 334 33.375 20.873 189.906 1.00 6.34 A ATOM 1541 CE3 TRP A 334 31.872 21.579 191.701 1.00 8.55 A ATOM 1542 CD1 TRP A 334 33.258 22.585 188.484 1.00 6.61 A ATOM 1543 NE1 TRP A 334 33.824 21.361 188.708 1.00 7.06 A ATOM 1544 CZ2 TRP A 334 33.673 19.655 190.557 1.00 6.77 A ATOM 1545 CZ3 TRP A 334 32.170 20.349 192.358 1.00 7.71 A ATOM 1546 CH2 TRP A 334 33.066 19.410 191.775 1.00 8.15 A ATOM 1547 C TRP A 334 33.820 25.538 189.647 1.00 7.38 A ATOM 1548 O TRP A 334 34.846 25.086 190.148 1.00 8.42 A ATOM 1549 N GLY A 335 33.773 26.146 188.455 1.00 7.12 A ATOM 1550 CA GLY A 335 34.967 26.385 187.650 1.00 6.28 A ATOM 1551 C GLY A 335 35.979 27.232 188.394 1.00 6.84 A ATOM 1552 O GLY A 335 37.180 26.946 188.365 1.00 6.62 A ATOM 1553 N LEU A 336 35.478 28.256 189.092 1.00 6.68 A ATOM 1554 CA LEU A 336 36.317 29.136 189.908 1.00 4.47 A ATOM 1555 CB LEU A 336 35.503 30.281 190.524 1.00 5.67 A ATOM 1556 CG LEU A 336 36.249 31.165 191.542 1.00 6.85 A ATOM 1557 CD1 LEU A 336 37.319 32.015 190.873 1.00 9.49 A ATOM 1558 CD2 LEU A 336 35.274 32.026 192.298 1.00 9.90 A ATOM 1559 C LEU A 336 36.945 28.277 191.008 1.00 5.28 A ATOM 1560 O LEU A 336 38.136 28.389 191.284 1.00 4.65 A ATOM 1561 N GLY A 337 36.152 27.351 191.546 1.00 5.39 A ATOM 1562 CA GLY A 337 36.630 26.446 192.582 1.00 5.35 A ATOM 1563 C GLY A 337 37.768 25.555 192.137 1.00 6.46 A ATOM 1564 O GLY A 337 38.736 25.374 192.878 1.00 6.24 A ATOM 1565 N VAL A 338 37.678 25.054 190.904 1.00 5.24 A ATOM 1566 CA VAL A 338 38.715 24.181 190.356 1.00 5.90 A ATOM 1567 CB VAL A 338 38.269 23.482 189.043 1.00 5.33 A ATOM 1568 CG1 VAL A 338 39.352 22.537 188.548 1.00 5.96 A ATOM 1569 CG2 VAL A 338 37.000 22.684 189.262 1.00 8.01 A ATOM 1570 C VAL A 338 40.033 24.940 190.151 1.00 6.00 A ATOM 1571 O VAL A 338 41.090 24.430 190.534 1.00 5.44 A ATOM 1572 N VAL A 339 39.970 26.163 189.611 1.00 6.37 A ATOM 1573 CA VAL A 339 41.197 26.950 189.404 1.00 6.09 A ATOM 1574 CB VAL A 339 41.043 28.145 188.402 1.00 6.11 A ATOM 1575 CG1 VAL A 339 40.624 27.634 187.045 1.00 8.57 A ATOM 1576 CG2 VAL A 339 40.086 29.206 188.899 1.00 11.74 A ATOM 1577 C VAL A 339 41.821 27.414 190.719 1.00 5.30 A ATOM 1578 O VAL A 339 43.038 27.415 190.853 1.00 6.78 A ATOM 1579 N MET A 340 40.978 27.735 191.704 1.00 7.84 A ATOM 1580 CA MET A 340 41.455 28.154 193.021 1.00 7.60 A ATOM 1581 CB MET A 340 40.314 28.718 193.873 1.00 9.80 A ATOM 1582 CG MET A 340 39.808 30.088 193.440 1.00 12.08 A ATOM 1583 SD MET A 340 41.050 31.377 193.499 1.00 15.52 A ATOM 1584 CE MET A 340 41.018 31.824 195.212 1.00 13.99 A ATOM 1585 C MET A 340 42.125 26.968 193.722 1.00 7.55 A ATOM 1586 O MET A 340 43.148 27.142 194.389 1.00 7.33 A ATOM 1587 N TYR A 341 41.591 25.762 193.486 1.00 7.78 A ATOM 1588 CA TYR A 341 42.139 24.525 194.050 1.00 7.21 A ATOM 1589 CB TYR A 341 41.183 23.327 193.830 1.00 7.22 A ATOM 1590 CG TYR A 341 41.578 22.049 194.561 1.00 7.96 A ATOM 1591 CD1 TYR A 341 42.624 21.231 194.079 1.00 7.01 A ATOM 1592 CE1 TYR A 341 43.029 20.068 194.756 1.00 8.21 A ATOM 1593 CD2 TYR A 341 40.933 21.661 195.750 1.00 7.56 A ATOM 1594 CE2 TYR A 341 41.331 20.478 196.447 1.00 7.60 A ATOM 1595 CZ TYR A 341 42.385 19.697 195.934 1.00 8.92 A ATOM 1596 OH TYR A 341 42.825 18.569 196.576 1.00 10.99 A ATOM 1597 C TYR A 341 43.509 24.272 193.417 1.00 6.78 A ATOM 1598 O TYR A 341 44.469 24.003 194.129 1.00 7.58 A ATOM 1599 N GLU A 342 43.596 24.390 192.091 1.00 6.47 A ATOM 1600 CA GLU A 342 44.858 24.197 191.375 1.00 7.82 A ATOM 1601 CB GLU A 342 44.659 24.355 189.876 1.00 6.70 A ATOM 1602 CG GLU A 342 43.909 23.227 189.232 1.00 8.49 A ATOM 1603 CD GLU A 342 43.719 23.466 187.763 1.00 10.87 A ATOM 1604 OE1 GLU A 342 42.866 24.302 187.416 1.00 8.48 A ATOM 1605 OE2 GLU A 342 44.435 22.842 186.954 1.00 10.15 A ATOM 1606 C GLU A 342 45.925 25.181 191.835 1.00 7.08 A ATOM 1607 O GLU A 342 47.084 24.805 192.023 1.00 7.82 A ATOM 1608 N MET A 343 45.515 26.434 192.040 1.00 9.08 A ATOM 1609 CA MET A 343 46.429 27.486 192.487 1.00 8.94 A ATOM 1610 CB MET A 343 45.786 28.872 192.360 1.00 9.73 A ATOM 1611 CG MET A 343 45.561 29.331 190.926 1.00 11.44 A ATOM 1612 SD MET A 343 45.208 31.100 190.816 1.00 13.16 A ATOM 1613 CE MET A 343 43.432 31.110 190.813 1.00 15.26 A ATOM 1614 C MET A 343 46.951 27.291 193.910 1.00 9.79 A ATOM 1615 O MET A 343 48.130 27.521 194.168 1.00 9.24 A ATOM 1616 N MET A 344 46.091 26.812 194.812 1.00 8.11 A ATOM 1617 CA MET A 344 46.486 26.626 196.213 1.00 9.92 A ATOM 1618 CB MET A 344 45.378 27.107 197.152 1.00 10.64 A ATOM 1619 CG MET A 344 45.118 28.579 197.021 1.00 11.26 A ATOM 1620 SD MET A 344 44.052 29.333 198.240 1.00 12.53 A ATOM 1621 CE MET A 344 42.443 28.833 197.665 1.00 14.60 A ATOM 1622 C MET A 344 46.951 25.242 196.629 1.00 10.10 A ATOM 1623 O MET A 344 47.716 25.113 197.594 1.00 11.04 A ATOM 1624 N CYS A 345 46.537 24.219 195.884 1.00 10.86 A ATOM 1625 CA CYS A 345 46.907 22.840 196.200 1.00 9.73 A ATOM 1626 CB CYS A 345 45.655 21.982 196.381 1.00 11.24 A ATOM 1627 SG CYS A 345 44.441 22.623 197.568 1.00 11.81 A ATOM 1628 C CYS A 345 47.864 22.195 195.193 1.00 9.70 A ATOM 1629 O CYS A 345 48.332 21.079 195.414 1.00 11.96 A ATOM 1630 N GLY A 346 48.140 22.893 194.090 1.00 10.45 A ATOM 1631 CA GLY A 346 49.078 22.401 193.085 1.00 10.92 A ATOM 1632 C GLY A 346 48.691 21.245 192.179 1.00 10.71 A ATOM 1633 O GLY A 346 49.561 20.638 191.549 1.00 13.43 A ATOM 1634 N ARG A 347 47.400 20.929 192.130 1.00 9.02 A ATOM 1635 CA ARG A 347 46.867 19.852 191.294 1.00 9.41 A ATOM 1636 CB ARG A 347 47.137 18.464 191.922 1.00 10.70 A ATOM 1637 CG ARG A 347 46.513 18.208 193.305 1.00 11.11 A ATOM 1638 CD ARG A 347 46.485 16.712 193.606 1.00 13.31 A ATOM 1639 NE ARG A 347 45.844 16.367 194.878 1.00 13.84 A ATOM 1640 CZ ARG A 347 44.553 16.069 195.031 1.00 16.02 A ATOM 1641 NH1 ARG A 347 43.723 16.087 193.993 1.00 16.77 A ATOM 1642 NH2 ARG A 347 44.098 15.692 196.221 1.00 15.24 A ATOM 1643 C ARG A 347 45.366 20.038 191.118 1.00 9.80 A ATOM 1644 O ARG A 347 44.742 20.818 191.839 1.00 7.76 A ATOM 1645 N LEU A 348 44.790 19.299 190.170 1.00 8.76 A ATOM 1646 CA LEU A 348 43.347 19.322 189.932 1.00 7.77 A ATOM 1647 CB LEU A 348 43.016 18.607 188.618 1.00 7.94 A ATOM 1648 CG LEU A 348 43.179 19.366 187.307 1.00 4.37 A ATOM 1649 CD1 LEU A 348 43.207 18.384 186.184 1.00 8.30 A ATOM 1650 CD2 LEU A 348 42.024 20.348 187.117 1.00 5.26 A ATOM 1651 C LEU A 348 42.691 18.556 191.080 1.00 8.12 A ATOM 1652 O LEU A 348 43.339 17.691 191.679 1.00 7.63 A ATOM 1653 N PRO A 349 41.445 18.918 191.467 1.00 6.62 A ATOM 1654 CD PRO A 349 40.641 20.102 191.103 1.00 7.65 A ATOM 1655 CA PRO A 349 40.799 18.176 192.562 1.00 8.62 A ATOM 1656 CB PRO A 349 39.548 19.012 192.863 1.00 8.60 A ATOM 1657 CG PRO A 349 39.268 19.720 191.564 1.00 6.96 A ATOM 1658 C PRO A 349 40.468 16.735 192.180 1.00 10.52 A ATOM 1659 O PRO A 349 40.465 15.844 193.035 1.00 12.38 A ATOM 1660 N PHE A 350 40.215 16.530 190.886 1.00 11.12 A ATOM 1661 CA PHE A 350 39.881 15.224 190.312 1.00 11.86 A ATOM 1662 CB PHE A 350 38.369 15.104 190.034 1.00 12.02 A ATOM 1663 CG PHE A 350 37.494 15.491 191.191 1.00 13.00 A ATOM 1664 CD1 PHE A 350 37.412 14.675 192.335 1.00 13.23 A ATOM 1665 CD2 PHE A 350 36.772 16.702 191.162 1.00 14.04 A ATOM 1666 CE1 PHE A 350 36.622 15.060 193.447 1.00 14.82 A ATOM 1667 CE2 PHE A 350 35.974 17.101 192.268 1.00 12.10 A ATOM 1668 CZ PHE A 350 35.902 16.274 193.412 1.00 13.30 A ATOM 1669 C PHE A 350 40.612 15.063 188.987 1.00 11.79 A ATOM 1670 O PHE A 350 40.535 15.948 188.125 1.00 10.18 A ATOM 1671 N TYR A 351 41.318 13.941 188.823 1.00 12.02 A ATOM 1672 CA TYR A 351 42.031 13.660 187.577 1.00 11.41 A ATOM 1673 CB TYR A 351 43.395 14.398 187.496 1.00 12.73 A ATOM 1674 CG TYR A 351 44.077 14.267 186.132 1.00 15.09 A ATOM 1675 CD1 TYR A 351 43.525 14.882 184.983 1.00 16.36 A ATOM 1676 CE1 TYR A 351 44.075 14.661 183.688 1.00 17.90 A ATOM 1677 CD2 TYR A 351 45.206 13.432 185.961 1.00 16.94 A ATOM 1678 CE2 TYR A 351 45.763 13.197 184.671 1.00 17.10 A ATOM 1679 CZ TYR A 351 45.189 13.813 183.545 1.00 18.68 A ATOM 1680 OH TYR A 351 45.705 13.567 182.296 1.00 19.38 A ATOM 1681 C TYR A 351 42.235 12.183 187.258 1.00 10.65 A ATOM 1682 O TYR A 351 42.535 11.370 188.133 1.00 9.83 A ATOM 1683 N ASN A 352 42.097 11.894 185.964 1.00 13.33 A ATOM 1684 CA ASN A 352 42.306 10.589 185.337 1.00 15.06 A ATOM 1685 CB ASN A 352 41.179 9.591 185.650 1.00 15.24 A ATOM 1686 CG ASN A 352 41.552 8.153 185.284 1.00 16.92 A ATOM 1687 OD1 ASN A 352 41.586 7.788 184.108 1.00 14.81 A ATOM 1688 ND2 ASN A 352 41.817 7.334 186.292 1.00 15.78 A ATOM 1689 C ASN A 352 42.358 10.881 183.833 1.00 16.14 A ATOM 1690 O ASN A 352 41.558 11.677 183.326 1.00 16.48 A ATOM 1691 N GLN A 353 43.292 10.233 183.130 1.00 18.24 A ATOM 1692 CA GLN A 353 43.475 10.398 181.678 1.00 20.68 A ATOM 1693 CB GLN A 353 44.721 9.636 181.194 1.00 23.71 A ATOM 1694 CG GLN A 353 44.775 8.154 181.584 1.00 29.95 A ATOM 1695 CD GLN A 353 45.429 7.286 180.527 1.00 33.80 A ATOM 1696 OE1 GLN A 353 46.598 7.473 180.183 1.00 37.41 A ATOM 1697 NE2 GLN A 353 44.672 6.326 180.003 1.00 34.96 A ATOM 1698 C GLN A 353 42.256 9.980 180.845 1.00 20.32 A ATOM 1699 O GLN A 353 42.007 10.530 179.769 1.00 21.84 A ATOM 1700 N ASP A 354 41.511 9.004 181.361 1.00 20.74 A ATOM 1701 CA ASP A 354 40.304 8.489 180.721 1.00 21.34 A ATOM 1702 CB ASP A 354 40.100 7.018 181.116 1.00 23.31 A ATOM 1703 CG ASP A 354 38.885 6.389 180.456 1.00 28.32 A ATOM 1704 OD1 ASP A 354 37.856 6.242 181.144 1.00 30.76 A ATOM 1705 OD2 ASP A 354 38.957 6.044 179.258 1.00 30.43 A ATOM 1706 C ASP A 354 39.139 9.360 181.198 1.00 19.72 A ATOM 1707 O ASP A 354 38.920 9.498 182.406 1.00 19.08 A ATOM 1708 N HIS A 355 38.411 9.944 180.245 1.00 19.58 A ATOM 1709 CA HIS A 355 37.271 10.820 180.536 1.00 19.39 A ATOM 1710 CB HIS A 355 36.764 11.511 179.263 1.00 19.77 A ATOM 1711 CG HIS A 355 37.698 12.551 178.715 1.00 19.38 A ATOM 1712 CD2 HIS A 355 38.764 13.182 179.265 1.00 17.83 A ATOM 1713 ND1 HIS A 355 37.578 13.052 177.436 1.00 21.90 A ATOM 1714 CE1 HIS A 355 38.529 13.944 177.222 1.00 21.76 A ATOM 1715 NE2 HIS A 355 39.262 14.042 178.316 1.00 20.76 A ATOM 1716 C HIS A 355 36.115 10.166 181.291 1.00 20.04 A ATOM 1717 O HIS A 355 35.514 10.805 182.154 1.00 18.52 A ATOM 1718 N GLU A 356 35.853 8.885 181.012 1.00 20.65 A ATOM 1719 CA GLU A 356 34.785 8.129 181.683 1.00 20.99 A ATOM 1720 CB GLU A 356 34.607 6.744 181.053 1.00 25.74 A ATOM 1721 CG GLU A 356 34.065 6.752 179.632 1.00 32.46 A ATOM 1722 CD GLU A 356 33.852 5.350 179.087 1.00 36.08 A ATOM 1723 OE1 GLU A 356 34.635 4.928 178.209 1.00 38.52 A ATOM 1724 OE2 GLU A 356 32.905 4.670 179.540 1.00 38.42 A ATOM 1725 C GLU A 356 35.060 7.975 183.181 1.00 18.43 A ATOM 1726 O GLU A 356 34.157 8.155 183.999 1.00 18.67 A ATOM 1727 N ARG A 357 36.322 7.704 183.527 1.00 15.83 A ATOM 1728 CA ARG A 357 36.748 7.552 184.923 1.00 15.71 A ATOM 1729 CB ARG A 357 38.129 6.894 185.014 1.00 16.68 A ATOM 1730 CG ARG A 357 38.264 5.485 184.432 1.00 19.52 A ATOM 1731 CD ARG A 357 37.563 4.407 185.263 1.00 23.41 A ATOM 1732 NE ARG A 357 36.140 4.264 184.944 1.00 28.97 A ATOM 1733 CZ ARG A 357 35.651 3.612 183.889 1.00 30.77 A ATOM 1734 NH1 ARG A 357 34.339 3.551 183.706 1.00 32.39 A ATOM 1735 NH2 ARG A 357 36.462 3.022 183.015 1.00 30.71 A ATOM 1736 C ARG A 357 36.791 8.913 185.618 1.00 11.47 A ATOM 1737 O ARG A 357 36.442 9.019 186.791 1.00 10.69 A ATOM 1738 N LEU A 358 37.172 9.948 184.862 1.00 11.53 A ATOM 1739 CA LEU A 358 37.248 11.334 185.356 1.00 10.03 A ATOM 1740 CB LEU A 358 37.860 12.243 184.278 1.00 10.92 A ATOM 1741 CG LEU A 358 37.811 13.775 184.369 1.00 10.43 A ATOM 1742 CD1 LEU A 358 38.723 14.289 185.482 1.00 11.85 A ATOM 1743 CD2 LEU A 358 38.202 14.353 183.034 1.00 12.77 A ATOM 1744 C LEU A 358 35.857 11.849 185.743 1.00 9.95 A ATOM 1745 O LEU A 358 35.699 12.506 186.771 1.00 8.78 A ATOM 1746 N PHE A 359 34.862 11.524 184.917 1.00 11.15 A ATOM 1747 CA PHE A 359 33.478 11.937 185.148 1.00 11.12 A ATOM 1748 CB PHE A 359 32.613 11.674 183.908 1.00 12.11 A ATOM 1749 CG PHE A 359 32.970 12.534 182.711 1.00 12.91 A ATOM 1750 CD1 PHE A 359 32.520 12.172 181.426 1.00 13.76 A ATOM 1751 CD2 PHE A 359 33.742 13.715 182.854 1.00 12.49 A ATOM 1752 CE1 PHE A 359 32.827 12.968 180.290 1.00 15.22 A ATOM 1753 CE2 PHE A 359 34.060 14.523 181.732 1.00 14.08 A ATOM 1754 CZ PHE A 359 33.601 14.150 180.443 1.00 15.66 A ATOM 1755 C PHE A 359 32.892 11.279 186.386 1.00 11.66 A ATOM 1756 O PHE A 359 32.102 11.898 187.099 1.00 12.57 A ATOM 1757 N GLU A 360 33.357 10.059 186.673 1.00 13.41 A ATOM 1758 CA GLU A 360 32.941 9.302 187.857 1.00 13.36 A ATOM 1759 CB GLU A 360 33.412 7.847 187.773 1.00 15.74 A ATOM 1760 CG GLU A 360 32.655 7.001 186.751 1.00 20.96 A ATOM 1761 CD GLU A 360 33.291 5.637 186.480 1.00 23.89 A ATOM 1762 OE1 GLU A 360 34.370 5.328 187.034 1.00 23.51 A ATOM 1763 OE2 GLU A 360 32.701 4.868 185.691 1.00 27.47 A ATOM 1764 C GLU A 360 33.539 9.970 189.095 1.00 12.15 A ATOM 1765 O GLU A 360 32.872 10.098 190.109 1.00 11.69 A ATOM 1766 N LEU A 361 34.772 10.462 188.971 1.00 10.17 A ATOM 1767 CA LEU A 361 35.449 11.148 190.076 1.00 9.58 A ATOM 1768 CB LEU A 361 36.927 11.391 189.747 1.00 9.91 A ATOM 1769 CG LEU A 361 37.869 10.187 189.621 1.00 11.80 A ATOM 1770 CD1 LEU A 361 39.220 10.671 189.133 1.00 12.73 A ATOM 1771 CD2 LEU A 361 38.015 9.450 190.951 1.00 12.04 A ATOM 1772 C LEU A 361 34.763 12.471 190.430 1.00 8.52 A ATOM 1773 O LEU A 361 34.522 12.745 191.601 1.00 9.51 A ATOM 1774 N ILE A 362 34.390 13.247 189.408 1.00 8.48 A ATOM 1775 CA ILE A 362 33.715 14.542 189.593 1.00 8.08 A ATOM 1776 CB ILE A 362 33.573 15.305 188.231 1.00 7.37 A ATOM 1777 CG2 ILE A 362 32.714 16.567 188.379 1.00 8.25 A ATOM 1778 CG1 ILE A 362 34.960 15.696 187.703 1.00 8.55 A ATOM 1779 CD1 ILE A 362 34.981 16.199 186.255 1.00 9.49 A ATOM 1780 C ILE A 362 32.340 14.370 190.264 1.00 7.15 A ATOM 1781 O ILE A 362 31.966 15.149 191.142 1.00 7.87 A ATOM 1782 N LEU A 363 31.629 13.320 189.870 1.00 8.80 A ATOM 1783 CA LEU A 363 30.311 13.028 190.416 1.00 9.50 A ATOM 1784 CB LEU A 363 29.511 12.163 189.433 1.00 10.23 A ATOM 1785 CG LEU A 363 28.866 12.756 188.183 1.00 11.66 A ATOM 1786 CD1 LEU A 363 28.563 11.635 187.201 1.00 12.67 A ATOM 1787 CD2 LEU A 363 27.597 13.511 188.547 1.00 11.57 A ATOM 1788 C LEU A 363 30.306 12.325 191.769 1.00 9.37 A ATOM 1789 O LEU A 363 29.470 12.638 192.611 1.00 9.29 A ATOM 1790 N MET A 364 31.270 11.424 191.991 1.00 12.17 A ATOM 1791 CA MET A 364 31.306 10.594 193.205 1.00 11.00 A ATOM 1792 CB MET A 364 31.343 9.103 192.817 1.00 12.91 A ATOM 1793 CG MET A 364 30.464 8.668 191.649 1.00 15.64 A ATOM 1794 SD MET A 364 28.732 8.949 191.931 1.00 17.28 A ATOM 1795 CE MET A 364 28.046 8.535 190.264 1.00 12.45 A ATOM 1796 C MET A 364 32.386 10.786 194.265 1.00 11.80 A ATOM 1797 O MET A 364 32.139 10.503 195.437 1.00 12.72 A ATOM 1798 N GLU A 365 33.586 11.193 193.858 1.00 9.97 A ATOM 1799 CA GLU A 365 34.700 11.343 194.802 1.00 11.91 A ATOM 1800 CB GLU A 365 36.043 11.191 194.062 1.00 11.49 A ATOM 1801 CG GLU A 365 37.295 11.013 194.941 1.00 16.42 A ATOM 1802 CD GLU A 365 37.255 9.748 195.789 1.00 18.10 A ATOM 1803 OE1 GLU A 365 37.645 8.678 195.278 1.00 21.84 A ATOM 1804 OE2 GLU A 365 36.827 9.828 196.961 1.00 19.20 A ATOM 1805 C GLU A 365 34.686 12.622 195.633 1.00 13.09 A ATOM 1806 O GLU A 365 34.324 13.687 195.141 1.00 12.98 A ATOM 1807 N GLU A 366 35.074 12.505 196.903 1.00 13.82 A ATOM 1808 CA GLU A 366 35.132 13.675 197.769 1.00 17.11 A ATOM 1809 CB GLU A 366 34.663 13.370 199.199 1.00 21.86 A ATOM 1810 CG GLU A 366 35.242 12.138 199.864 1.00 27.09 A ATOM 1811 CD GLU A 366 34.590 11.863 201.211 1.00 31.54 A ATOM 1812 OE1 GLU A 366 33.555 11.158 201.244 1.00 34.18 A ATOM 1813 OE2 GLU A 366 35.105 12.362 202.236 1.00 33.66 A ATOM 1814 C GLU A 366 36.511 14.327 197.736 1.00 16.12 A ATOM 1815 O GLU A 366 37.535 13.649 197.578 1.00 15.84 A ATOM 1816 N ILE A 367 36.503 15.657 197.786 1.00 16.03 A ATOM 1817 CA ILE A 367 37.711 16.482 197.759 1.00 16.93 A ATOM 1818 CB ILE A 367 37.386 17.986 197.547 1.00 18.85 A ATOM 1819 CG2 ILE A 367 37.265 18.290 196.058 1.00 19.99 A ATOM 1820 CG1 ILE A 367 36.154 18.392 198.376 1.00 22.24 A ATOM 1821 CD1 ILE A 367 35.726 19.831 198.234 1.00 26.50 A ATOM 1822 C ILE A 367 38.569 16.353 199.010 1.00 16.24 A ATOM 1823 O ILE A 367 38.057 16.146 200.114 1.00 16.79 A ATOM 1824 N ARG A 368 39.881 16.417 198.797 1.00 14.71 A ATOM 1825 CA ARG A 368 40.867 16.333 199.868 1.00 14.98 A ATOM 1826 CB ARG A 368 41.783 15.129 199.657 1.00 15.28 A ATOM 1827 CG ARG A 368 41.061 13.796 199.810 1.00 16.96 A ATOM 1828 CD ARG A 368 41.968 12.615 199.551 1.00 15.72 A ATOM 1829 NE ARG A 368 43.020 12.464 200.558 1.00 13.71 A ATOM 1830 CZ ARG A 368 42.860 11.897 201.753 1.00 14.25 A ATOM 1831 NH1 ARG A 368 41.674 11.425 202.130 1.00 12.11 A ATOM 1832 NH2 ARG A 368 43.910 11.730 202.548 1.00 13.19 A ATOM 1833 C ARG A 368 41.667 17.626 199.887 1.00 13.16 A ATOM 1834 O ARG A 368 41.797 18.288 198.859 1.00 14.99 A ATOM 1835 N PHE A 369 42.154 18.009 201.065 1.00 11.72 A ATOM 1836 CA PHE A 369 42.919 19.247 201.232 1.00 12.56 A ATOM 1837 CB PHE A 369 42.124 20.266 202.075 1.00 14.44 A ATOM 1838 CG PHE A 369 40.806 20.660 201.492 1.00 16.74 A ATOM 1839 CD1 PHE A 369 40.740 21.329 200.255 1.00 16.87 A ATOM 1840 CD2 PHE A 369 39.615 20.357 202.175 1.00 18.15 A ATOM 1841 CE1 PHE A 369 39.497 21.691 199.700 1.00 17.51 A ATOM 1842 CE2 PHE A 369 38.355 20.715 201.635 1.00 17.80 A ATOM 1843 CZ PHE A 369 38.298 21.385 200.391 1.00 18.34 A ATOM 1844 C PHE A 369 44.214 19.014 201.988 1.00 10.89 A ATOM 1845 O PHE A 369 44.244 18.175 202.892 1.00 9.62 A ATOM 1846 N PRO A 370 45.297 19.767 201.654 1.00 11.55 A ATOM 1847 CD PRO A 370 45.486 20.615 200.458 1.00 9.99 A ATOM 1848 CA PRO A 370 46.577 19.614 202.364 1.00 11.45 A ATOM 1849 CB PRO A 370 47.493 20.586 201.619 1.00 13.59 A ATOM 1850 CG PRO A 370 46.972 20.535 200.234 1.00 12.44 A ATOM 1851 C PRO A 370 46.351 20.084 203.810 1.00 13.02 A ATOM 1852 O PRO A 370 45.597 21.036 204.030 1.00 11.71 A ATOM 1853 N ARG A 371 46.941 19.389 204.787 1.00 12.92 A ATOM 1854 CA ARG A 371 46.782 19.735 206.213 1.00 15.39 A ATOM 1855 CB ARG A 371 47.612 18.794 207.093 1.00 15.08 A ATOM 1856 CG ARG A 371 47.102 17.378 207.153 1.00 17.29 A ATOM 1857 CD ARG A 371 48.043 16.473 207.934 1.00 18.11 A ATOM 1858 NE ARG A 371 47.703 15.060 207.764 1.00 19.41 A ATOM 1859 CZ ARG A 371 46.831 14.385 208.512 1.00 21.94 A ATOM 1860 NH1 ARG A 371 46.185 14.978 209.509 1.00 23.13 A ATOM 1861 NH2 ARG A 371 46.603 13.103 208.258 1.00 21.92 A ATOM 1862 C ARG A 371 47.138 21.175 206.581 1.00 16.98 A ATOM 1863 O ARG A 371 46.508 21.774 207.465 1.00 17.84 A ATOM 1864 N THR A 372 48.110 21.726 205.853 1.00 16.72 A ATOM 1865 CA THR A 372 48.626 23.078 206.065 1.00 19.70 A ATOM 1866 CB THR A 372 50.095 23.187 205.598 1.00 20.96 A ATOM 1867 OG1 THR A 372 50.191 22.808 204.218 1.00 23.21 A ATOM 1868 CG2 THR A 372 50.990 22.289 206.443 1.00 23.38 A ATOM 1869 C THR A 372 47.828 24.221 205.441 1.00 18.26 A ATOM 1870 O THR A 372 48.093 25.391 205.739 1.00 20.19 A ATOM 1871 N LEU A 373 46.867 23.887 204.575 1.00 16.85 A ATOM 1872 CA LEU A 373 46.012 24.889 203.923 1.00 14.74 A ATOM 1873 CB LEU A 373 45.106 24.214 202.880 1.00 15.58 A ATOM 1874 CG LEU A 373 44.364 25.061 201.836 1.00 15.64 A ATOM 1875 CD1 LEU A 373 45.348 25.795 200.934 1.00 14.61 A ATOM 1876 CD2 LEU A 373 43.437 24.181 201.004 1.00 13.80 A ATOM 1877 C LEU A 373 45.182 25.570 205.023 1.00 14.73 A ATOM 1878 O LEU A 373 44.702 24.905 205.944 1.00 15.24 A ATOM 1879 N SER A 374 45.093 26.897 204.968 1.00 14.03 A ATOM 1880 CA SER A 374 44.361 27.677 205.970 1.00 13.90 A ATOM 1881 CB SER A 374 44.510 29.174 205.682 1.00 15.68 A ATOM 1882 OG SER A 374 43.662 29.580 204.620 1.00 14.80 A ATOM 1883 C SER A 374 42.877 27.295 206.038 1.00 14.54 A ATOM 1884 O SER A 374 42.316 26.860 205.022 1.00 12.11 A ATOM 1885 N PRO A 375 42.240 27.391 207.236 1.00 13.75 A ATOM 1886 CD PRO A 375 42.799 27.643 208.581 1.00 16.61 A ATOM 1887 CA PRO A 375 40.817 27.039 207.346 1.00 14.78 A ATOM 1888 CB PRO A 375 40.517 27.242 208.841 1.00 15.76 A ATOM 1889 CG PRO A 375 41.608 28.168 209.316 1.00 17.77 A ATOM 1890 C PRO A 375 39.888 27.848 206.438 1.00 13.92 A ATOM 1891 O PRO A 375 38.910 27.307 205.921 1.00 13.54 A ATOM 1892 N GLU A 376 40.252 29.109 206.182 1.00 14.21 A ATOM 1893 CA GLU A 376 39.459 29.983 205.312 1.00 15.69 A ATOM 1894 CB GLU A 376 39.838 31.467 205.490 1.00 16.80 A ATOM 1895 CG GLU A 376 41.287 31.862 205.168 1.00 18.90 A ATOM 1896 CD GLU A 376 42.206 31.939 206.388 1.00 21.53 A ATOM 1897 OE1 GLU A 376 41.923 31.296 207.429 1.00 18.38 A ATOM 1898 OE2 GLU A 376 43.248 32.631 206.282 1.00 20.98 A ATOM 1899 C GLU A 376 39.544 29.551 203.841 1.00 14.26 A ATOM 1900 O GLU A 376 38.574 29.698 203.096 1.00 13.81 A ATOM 1901 N ALA A 377 40.687 28.976 203.456 1.00 13.24 A ATOM 1902 CA ALA A 377 40.898 28.485 202.092 1.00 12.78 A ATOM 1903 CB ALA A 377 42.373 28.352 201.781 1.00 12.35 A ATOM 1904 C ALA A 377 40.179 27.158 201.911 1.00 11.93 A ATOM 1905 O ALA A 377 39.515 26.962 200.901 1.00 10.02 A ATOM 1906 N LYS A 378 40.246 26.295 202.932 1.00 11.91 A ATOM 1907 CA LYS A 378 39.566 24.992 202.919 1.00 12.33 A ATOM 1908 CB LYS A 378 39.853 24.199 204.198 1.00 12.06 A ATOM 1909 CG LYS A 378 41.248 23.631 204.286 1.00 15.67 A ATOM 1910 CD LYS A 378 41.458 22.874 205.584 1.00 17.02 A ATOM 1911 CE LYS A 378 42.851 22.276 205.633 1.00 16.73 A ATOM 1912 NZ LYS A 378 43.160 21.642 206.940 1.00 21.03 A ATOM 1913 C LYS A 378 38.060 25.195 202.798 1.00 12.05 A ATOM 1914 O LYS A 378 37.397 24.477 202.052 1.00 11.83 A ATOM 1915 N SER A 379 37.556 26.224 203.490 1.00 11.10 A ATOM 1916 CA SER A 379 36.134 26.582 203.490 1.00 11.67 A ATOM 1917 CB SER A 379 35.828 27.582 204.611 1.00 12.32 A ATOM 1918 OG SER A 379 34.457 27.948 204.619 1.00 13.54 A ATOM 1919 C SER A 379 35.686 27.149 202.142 1.00 10.66 A ATOM 1920 O SER A 379 34.587 26.833 201.677 1.00 9.95 A ATOM 1921 N LEU A 380 36.546 27.958 201.515 1.00 11.69 A ATOM 1922 CA LEU A 380 36.244 28.549 200.203 1.00 9.61 A ATOM 1923 CB LEU A 380 37.325 29.546 199.767 1.00 11.07 A ATOM 1924 CG LEU A 380 37.030 30.229 198.419 1.00 10.92 A ATOM 1925 CD1 LEU A 380 36.093 31.405 198.603 1.00 13.48 A ATOM 1926 CD2 LEU A 380 38.301 30.646 197.733 1.00 10.36 A ATOM 1927 C LEU A 380 36.132 27.446 199.159 1.00 9.94 A ATOM 1928 O LEU A 380 35.135 27.369 198.440 1.00 10.00 A ATOM 1929 N LEU A 381 37.136 26.569 199.142 1.00 9.86 A ATOM 1930 CA LEU A 381 37.191 25.456 198.202 1.00 9.46 A ATOM 1931 CB LEU A 381 38.570 24.799 198.221 1.00 9.84 A ATOM 1932 CG LEU A 381 39.744 25.697 197.831 1.00 9.17 A ATOM 1933 CD1 LEU A 381 41.052 24.948 197.958 1.00 9.01 A ATOM 1934 CD2 LEU A 381 39.548 26.208 196.420 1.00 11.76 A ATOM 1935 C LEU A 381 36.089 24.436 198.415 1.00 10.95 A ATOM 1936 O LEU A 381 35.477 24.006 197.449 1.00 10.54 A ATOM 1937 N ALA A 382 35.775 24.129 199.677 1.00 11.73 A ATOM 1938 CA ALA A 382 34.698 23.183 200.007 1.00 12.27 A ATOM 1939 CB ALA A 382 34.693 22.870 201.498 1.00 12.71 A ATOM 1940 C ALA A 382 33.342 23.749 199.579 1.00 12.03 A ATOM 1941 O ALA A 382 32.472 23.007 199.117 1.00 12.69 A ATOM 1942 N GLY A 383 33.222 25.078 199.658 1.00 10.59 A ATOM 1943 CA GLY A 383 32.001 25.772 199.280 1.00 10.18 A ATOM 1944 C GLY A 383 31.814 25.873 197.775 1.00 8.45 A ATOM 1945 O GLY A 383 30.723 25.612 197.272 1.00 10.40 A ATOM 1946 N LEU A 384 32.876 26.254 197.062 1.00 7.94 A ATOM 1947 CA LEU A 384 32.837 26.384 195.604 1.00 8.03 A ATOM 1948 CB LEU A 384 34.056 27.159 195.096 1.00 5.65 A ATOM 1949 CG LEU A 384 34.172 28.658 195.399 1.00 7.76 A ATOM 1950 CD1 LEU A 384 35.550 29.149 195.002 1.00 6.46 A ATOM 1951 CD2 LEU A 384 33.102 29.457 194.674 1.00 6.17 A ATOM 1952 C LEU A 384 32.764 25.013 194.933 1.00 8.59 A ATOM 1953 O LEU A 384 32.134 24.863 193.884 1.00 9.89 A ATOM 1954 N LEU A 385 33.365 24.013 195.578 1.00 8.39 A ATOM 1955 CA LEU A 385 33.369 22.650 195.061 1.00 9.22 A ATOM 1956 CB LEU A 385 34.774 22.025 195.118 1.00 9.16 A ATOM 1957 CG LEU A 385 35.851 22.686 194.247 1.00 9.77 A ATOM 1958 CD1 LEU A 385 37.221 22.141 194.588 1.00 9.20 A ATOM 1959 CD2 LEU A 385 35.543 22.492 192.770 1.00 10.49 A ATOM 1960 C LEU A 385 32.306 21.712 195.640 1.00 9.48 A ATOM 1961 O LEU A 385 32.472 20.490 195.649 1.00 9.86 A ATOM 1962 N LYS A 386 31.188 22.287 196.079 1.00 10.56 A ATOM 1963 CA LYS A 386 30.071 21.493 196.591 1.00 11.38 A ATOM 1964 CB LYS A 386 29.109 22.372 197.388 1.00 14.55 A ATOM 1965 CG LYS A 386 28.256 21.629 198.398 1.00 20.84 A ATOM 1966 CD LYS A 386 28.988 21.414 199.715 1.00 22.83 A ATOM 1967 CE LYS A 386 28.062 20.811 200.756 1.00 27.84 A ATOM 1968 NZ LYS A 386 28.721 20.676 202.085 1.00 29.09 A ATOM 1969 C LYS A 386 29.389 20.955 195.330 1.00 10.45 A ATOM 1970 O LYS A 386 29.172 21.711 194.373 1.00 9.32 A ATOM 1971 N LYS A 387 29.093 19.655 195.320 1.00 10.89 A ATOM 1972 CA LYS A 387 28.487 18.999 194.159 1.00 12.50 A ATOM 1973 CB LYS A 387 28.544 17.477 194.306 1.00 12.97 A ATOM 1974 CG LYS A 387 29.971 16.958 194.448 1.00 13.15 A ATOM 1975 CD LYS A 387 30.063 15.475 194.194 1.00 12.93 A ATOM 1976 CE LYS A 387 31.405 14.919 194.638 1.00 11.17 A ATOM 1977 NZ LYS A 387 32.570 15.446 193.861 1.00 12.25 A ATOM 1978 C LYS A 387 27.095 19.470 193.759 1.00 13.09 A ATOM 1979 O LYS A 387 26.813 19.609 192.568 1.00 12.47 A ATOM 1980 N ASP A 388 26.258 19.762 194.754 1.00 12.54 A ATOM 1981 CA ASP A 388 24.898 20.257 194.532 1.00 13.42 A ATOM 1982 CB ASP A 388 24.025 19.933 195.765 1.00 16.51 A ATOM 1983 CG ASP A 388 22.566 20.410 195.637 1.00 18.40 A ATOM 1984 OD1 ASP A 388 22.161 20.968 194.596 1.00 17.40 A ATOM 1985 OD2 ASP A 388 21.814 20.229 196.614 1.00 18.24 A ATOM 1986 C ASP A 388 24.991 21.778 194.298 1.00 13.09 A ATOM 1987 O ASP A 388 25.468 22.507 195.176 1.00 11.21 A ATOM 1988 N PRO A 389 24.549 22.268 193.109 1.00 13.98 A ATOM 1989 CD PRO A 389 24.071 21.528 191.924 1.00 13.65 A ATOM 1990 CA PRO A 389 24.602 23.708 192.813 1.00 14.34 A ATOM 1991 CB PRO A 389 24.052 23.802 191.384 1.00 14.48 A ATOM 1992 CG PRO A 389 23.236 22.563 191.219 1.00 14.86 A ATOM 1993 C PRO A 389 23.830 24.586 193.797 1.00 14.54 A ATOM 1994 O PRO A 389 24.250 25.703 194.076 1.00 15.08 A ATOM 1995 N LYS A 390 22.772 24.030 194.391 1.00 16.14 A ATOM 1996 CA LYS A 390 21.954 24.748 195.371 1.00 19.29 A ATOM 1997 CB LYS A 390 20.614 24.041 195.577 1.00 20.74 A ATOM 1998 CG LYS A 390 19.617 24.294 194.464 1.00 25.04 A ATOM 1999 CD LYS A 390 18.218 23.864 194.877 1.00 30.99 A ATOM 2000 CE LYS A 390 17.159 24.495 193.984 1.00 33.33 A ATOM 2001 NZ LYS A 390 17.119 25.984 194.123 1.00 35.42 A ATOM 2002 C LYS A 390 22.652 24.955 196.721 1.00 18.60 A ATOM 2003 O LYS A 390 22.353 25.915 197.435 1.00 21.49 A ATOM 2004 N GLN A 391 23.586 24.060 197.050 1.00 18.57 A ATOM 2005 CA GLN A 391 24.353 24.123 198.300 1.00 19.12 A ATOM 2006 CB GLN A 391 24.591 22.709 198.856 1.00 20.95 A ATOM 2007 CG GLN A 391 23.347 21.934 199.310 1.00 25.46 A ATOM 2008 CD GLN A 391 23.656 20.476 199.664 1.00 28.32 A ATOM 2009 OE1 GLN A 391 24.492 20.193 200.526 1.00 31.25 A ATOM 2010 NE2 GLN A 391 22.977 19.547 198.996 1.00 28.41 A ATOM 2011 C GLN A 391 25.712 24.816 198.084 1.00 16.92 A ATOM 2012 O GLN A 391 26.411 25.145 199.046 1.00 17.18 A ATOM 2013 N ARG A 392 26.061 25.054 196.817 1.00 14.27 A ATOM 2014 CA ARG A 392 27.332 25.685 196.435 1.00 11.83 A ATOM 2015 CB ARG A 392 27.594 25.446 194.939 1.00 10.55 A ATOM 2016 CG ARG A 392 28.962 25.900 194.406 1.00 9.50 A ATOM 2017 CD ARG A 392 29.137 25.565 192.933 1.00 8.08 A ATOM 2018 NE ARG A 392 28.943 24.135 192.703 1.00 8.88 A ATOM 2019 CZ ARG A 392 28.373 23.609 191.625 1.00 8.90 A ATOM 2020 NH1 ARG A 392 27.947 24.387 190.638 1.00 9.41 A ATOM 2021 NH2 ARG A 392 28.133 22.304 191.586 1.00 9.77 A ATOM 2022 C ARG A 392 27.419 27.175 196.748 1.00 10.82 A ATOM 2023 O ARG A 392 26.407 27.881 196.711 1.00 11.58 A ATOM 2024 N LEU A 393 28.635 27.630 197.073 1.00 10.59 A ATOM 2025 CA LEU A 393 28.919 29.035 197.361 1.00 11.25 A ATOM 2026 CB LEU A 393 30.336 29.191 197.918 1.00 12.85 A ATOM 2027 CG LEU A 393 30.767 30.542 198.479 1.00 13.61 A ATOM 2028 CD1 LEU A 393 30.120 30.783 199.841 1.00 14.74 A ATOM 2029 CD2 LEU A 393 32.276 30.576 198.592 1.00 13.30 A ATOM 2030 C LEU A 393 28.784 29.779 196.033 1.00 13.13 A ATOM 2031 O LEU A 393 29.526 29.519 195.077 1.00 13.97 A ATOM 2032 N GLY A 394 27.768 30.631 195.967 1.00 12.66 A ATOM 2033 CA GLY A 394 27.484 31.381 194.760 1.00 12.06 A ATOM 2034 C GLY A 394 26.319 30.763 194.013 1.00 12.94 A ATOM 2035 O GLY A 394 25.881 31.299 192.994 1.00 14.02 A ATOM 2036 N GLY A 395 25.828 29.635 194.529 1.00 15.17 A ATOM 2037 CA GLY A 395 24.720 28.915 193.919 1.00 16.80 A ATOM 2038 C GLY A 395 23.344 29.380 194.350 1.00 17.44 A ATOM 2039 O GLY A 395 22.337 28.932 193.798 1.00 18.42 A ATOM 2040 N GLY A 396 23.311 30.280 195.334 1.00 18.62 A ATOM 2041 CA GLY A 396 22.061 30.829 195.836 1.00 18.72 A ATOM 2042 C GLY A 396 21.583 31.999 194.987 1.00 20.09 A ATOM 2043 O GLY A 396 22.287 32.380 194.044 1.00 19.22 A ATOM 2044 N PRO A 397 20.409 32.604 195.288 1.00 21.16 A ATOM 2045 CD PRO A 397 19.443 32.168 196.317 1.00 22.25 A ATOM 2046 CA PRO A 397 19.856 33.739 194.531 1.00 21.11 A ATOM 2047 CB PRO A 397 18.560 34.045 195.282 1.00 21.67 A ATOM 2048 CG PRO A 397 18.142 32.708 195.781 1.00 23.33 A ATOM 2049 C PRO A 397 20.739 34.989 194.413 1.00 20.15 A ATOM 2050 O PRO A 397 20.646 35.720 193.420 1.00 19.90 A ATOM 2051 N SER A 398 21.609 35.215 195.402 1.00 19.97 A ATOM 2052 CA SER A 398 22.497 36.384 195.395 1.00 17.27 A ATOM 2053 CB SER A 398 22.865 36.807 196.820 1.00 19.31 A ATOM 2054 OG SER A 398 23.582 35.796 197.497 1.00 24.32 A ATOM 2055 C SER A 398 23.747 36.231 194.522 1.00 16.60 A ATOM 2056 O SER A 398 24.508 37.187 194.351 1.00 15.27 A ATOM 2057 N ASP A 399 23.946 35.022 193.986 1.00 16.68 A ATOM 2058 CA ASP A 399 25.052 34.685 193.078 1.00 14.61 A ATOM 2059 CB ASP A 399 24.739 35.277 191.685 1.00 15.21 A ATOM 2060 CG ASP A 399 25.636 34.738 190.580 1.00 17.81 A ATOM 2061 OD1 ASP A 399 25.662 33.511 190.348 1.00 15.72 A ATOM 2062 OD2 ASP A 399 26.295 35.569 189.929 1.00 19.60 A ATOM 2063 C ASP A 399 26.459 35.068 193.592 1.00 13.28 A ATOM 2064 O ASP A 399 26.909 34.534 194.602 1.00 12.10 A ATOM 2065 N ALA A 400 27.098 36.045 192.946 1.00 14.41 A ATOM 2066 CA ALA A 400 28.443 36.501 193.297 1.00 12.16 A ATOM 2067 CB ALA A 400 28.916 37.510 192.298 1.00 12.22 A ATOM 2068 C ALA A 400 28.636 37.042 194.702 1.00 12.25 A ATOM 2069 O ALA A 400 29.732 36.926 195.252 1.00 10.75 A ATOM 2070 N LYS A 401 27.566 37.592 195.284 1.00 11.70 A ATOM 2071 CA LYS A 401 27.602 38.157 196.634 1.00 13.89 A ATOM 2072 CB LYS A 401 26.241 38.751 197.017 1.00 16.12 A ATOM 2073 CG LYS A 401 26.271 39.596 198.286 1.00 19.60 A ATOM 2074 CD LYS A 401 24.880 39.905 198.794 1.00 20.68 A ATOM 2075 CE LYS A 401 24.950 40.615 200.133 1.00 22.34 A ATOM 2076 NZ LYS A 401 23.598 40.943 200.648 1.00 25.16 A ATOM 2077 C LYS A 401 28.053 37.138 197.680 1.00 14.23 A ATOM 2078 O LYS A 401 28.843 37.475 198.559 1.00 14.96 A ATOM 2079 N GLU A 402 27.611 35.886 197.528 1.00 13.34 A ATOM 2080 CA GLU A 402 27.979 34.802 198.448 1.00 15.47 A ATOM 2081 CB GLU A 402 27.203 33.525 198.123 1.00 16.98 A ATOM 2082 CG GLU A 402 25.721 33.597 198.471 1.00 22.80 A ATOM 2083 CD GLU A 402 24.948 32.320 198.157 1.00 26.41 A ATOM 2084 OE1 GLU A 402 25.359 31.553 197.259 1.00 26.03 A ATOM 2085 OE2 GLU A 402 23.905 32.091 198.809 1.00 27.43 A ATOM 2086 C GLU A 402 29.484 34.519 198.430 1.00 14.42 A ATOM 2087 O GLU A 402 30.088 34.282 199.480 1.00 13.65 A ATOM 2088 N VAL A 403 30.082 34.607 197.239 1.00 13.01 A ATOM 2089 CA VAL A 403 31.518 34.385 197.053 1.00 11.76 A ATOM 2090 CB VAL A 403 31.876 34.137 195.560 1.00 11.44 A ATOM 2091 CG1 VAL A 403 33.369 33.820 195.403 1.00 9.58 A ATOM 2092 CG2 VAL A 403 31.043 32.986 195.005 1.00 11.72 A ATOM 2093 C VAL A 403 32.303 35.588 197.576 1.00 11.84 A ATOM 2094 O VAL A 403 33.286 35.420 198.298 1.00 10.47 A ATOM 2095 N MET A 404 31.830 36.787 197.232 1.00 11.80 A ATOM 2096 CA MET A 404 32.457 38.045 197.641 1.00 13.26 A ATOM 2097 CB MET A 404 31.750 39.244 196.994 1.00 15.05 A ATOM 2098 CG MET A 404 31.958 39.354 195.494 1.00 16.33 A ATOM 2099 SD MET A 404 31.462 40.933 194.791 1.00 18.23 A ATOM 2100 CE MET A 404 29.757 40.696 194.547 1.00 21.53 A ATOM 2101 C MET A 404 32.516 38.250 199.151 1.00 13.67 A ATOM 2102 O MET A 404 33.516 38.754 199.671 1.00 13.54 A ATOM 2103 N GLU A 405 31.466 37.801 199.840 1.00 14.50 A ATOM 2104 CA GLU A 405 31.359 37.928 201.291 1.00 14.98 A ATOM 2105 CB GLU A 405 29.903 38.193 201.706 1.00 17.47 A ATOM 2106 CG GLU A 405 29.295 39.491 201.149 1.00 23.07 A ATOM 2107 CD GLU A 405 30.138 40.735 201.417 1.00 27.01 A ATOM 2108 OE1 GLU A 405 30.342 41.086 202.601 1.00 30.41 A ATOM 2109 OE2 GLU A 405 30.600 41.358 200.436 1.00 29.99 A ATOM 2110 C GLU A 405 31.954 36.790 202.119 1.00 13.80 A ATOM 2111 O GLU A 405 31.878 36.817 203.349 1.00 14.06 A ATOM 2112 N HIS A 406 32.587 35.819 201.455 1.00 11.75 A ATOM 2113 CA HIS A 406 33.219 34.694 202.155 1.00 11.72 A ATOM 2114 CB HIS A 406 33.585 33.576 201.166 1.00 11.05 A ATOM 2115 CG HIS A 406 34.070 32.324 201.828 1.00 11.80 A ATOM 2116 CD2 HIS A 406 33.421 31.187 202.176 1.00 11.83 A ATOM 2117 ND1 HIS A 406 35.361 32.184 202.289 1.00 11.13 A ATOM 2118 CE1 HIS A 406 35.484 31.021 202.901 1.00 12.32 A ATOM 2119 NE2 HIS A 406 34.321 30.396 202.846 1.00 10.29 A ATOM 2120 C HIS A 406 34.466 35.203 202.902 1.00 11.51 A ATOM 2121 O HIS A 406 35.166 36.089 202.404 1.00 11.68 A ATOM 2122 N ARG A 407 34.731 34.636 204.084 1.00 13.02 A ATOM 2123 CA ARG A 407 35.868 35.036 204.933 1.00 14.27 A ATOM 2124 CB ARG A 407 35.863 34.286 206.275 1.00 16.28 A ATOM 2125 CG ARG A 407 35.775 32.776 206.190 1.00 22.36 A ATOM 2126 CD ARG A 407 35.703 32.149 207.573 1.00 26.72 A ATOM 2127 NE ARG A 407 35.227 30.767 207.515 1.00 31.71 A ATOM 2128 CZ ARG A 407 35.868 29.715 208.020 1.00 33.50 A ATOM 2129 NH1 ARG A 407 37.038 29.859 208.635 1.00 35.91 A ATOM 2130 NH2 ARG A 407 35.326 28.509 207.922 1.00 34.67 A ATOM 2131 C ARG A 407 37.259 35.005 204.297 1.00 12.73 A ATOM 2132 O ARG A 407 38.146 35.746 204.718 1.00 13.98 A ATOM 2133 N PHE A 408 37.424 34.196 203.248 1.00 12.68 A ATOM 2134 CA PHE A 408 38.694 34.107 202.521 1.00 12.92 A ATOM 2135 CB PHE A 408 38.625 32.985 201.467 1.00 10.80 A ATOM 2136 CG PHE A 408 39.886 32.820 200.656 1.00 13.01 A ATOM 2137 CD1 PHE A 408 40.999 32.147 201.191 1.00 13.20 A ATOM 2138 CD2 PHE A 408 39.973 33.352 199.356 1.00 12.18 A ATOM 2139 CE1 PHE A 408 42.199 32.001 200.441 1.00 13.70 A ATOM 2140 CE2 PHE A 408 41.159 33.217 198.594 1.00 14.00 A ATOM 2141 CZ PHE A 408 42.277 32.540 199.137 1.00 13.44 A ATOM 2142 C PHE A 408 39.002 35.455 201.853 1.00 11.74 A ATOM 2143 O PHE A 408 40.166 35.818 201.692 1.00 13.32 A ATOM 2144 N PHE A 409 37.945 36.180 201.486 1.00 11.79 A ATOM 2145 CA PHE A 409 38.060 37.477 200.826 1.00 11.95 A ATOM 2146 CB PHE A 409 37.098 37.537 199.629 1.00 12.23 A ATOM 2147 CG PHE A 409 37.473 36.630 198.481 1.00 10.69 A ATOM 2148 CD1 PHE A 409 36.592 35.616 198.066 1.00 10.42 A ATOM 2149 CD2 PHE A 409 38.687 36.806 197.782 1.00 11.00 A ATOM 2150 CE1 PHE A 409 36.909 34.776 196.957 1.00 10.74 A ATOM 2151 CE2 PHE A 409 39.023 35.976 196.670 1.00 10.99 A ATOM 2152 CZ PHE A 409 38.128 34.959 196.258 1.00 9.34 A ATOM 2153 C PHE A 409 37.804 38.682 201.745 1.00 13.98 A ATOM 2154 O PHE A 409 37.555 39.786 201.255 1.00 13.33 A ATOM 2155 N LEU A 410 37.906 38.482 203.063 1.00 13.39 A ATOM 2156 CA LEU A 410 37.678 39.547 204.058 1.00 16.53 A ATOM 2157 CB LEU A 410 37.848 38.989 205.482 1.00 20.16 A ATOM 2158 CG LEU A 410 37.432 39.810 206.716 1.00 23.30 A ATOM 2159 CD1 LEU A 410 35.917 39.992 206.765 1.00 25.76 A ATOM 2160 CD2 LEU A 410 37.913 39.103 207.973 1.00 26.00 A ATOM 2161 C LEU A 410 38.561 40.796 203.871 1.00 17.65 A ATOM 2162 O LEU A 410 38.076 41.926 203.997 1.00 19.37 A ATOM 2163 N SER A 411 39.820 40.577 203.484 1.00 18.04 A ATOM 2164 CA SER A 411 40.798 41.652 203.269 1.00 19.59 A ATOM 2165 CB SER A 411 42.221 41.105 203.458 1.00 21.68 A ATOM 2166 OG SER A 411 42.528 40.102 202.496 1.00 23.38 A ATOM 2167 C SER A 411 40.689 42.353 201.907 1.00 19.99 A ATOM 2168 O SER A 411 41.476 43.254 201.598 1.00 21.28 A ATOM 2169 N ILE A 412 39.704 41.945 201.111 1.00 18.60 A ATOM 2170 CA ILE A 412 39.493 42.500 199.777 1.00 18.28 A ATOM 2171 CB ILE A 412 39.151 41.357 198.742 1.00 18.49 A ATOM 2172 CG2 ILE A 412 38.813 41.920 197.364 1.00 18.91 A ATOM 2173 CG1 ILE A 412 40.297 40.335 198.643 1.00 18.27 A ATOM 2174 CD1 ILE A 412 41.629 40.866 198.097 1.00 19.98 A ATOM 2175 C ILE A 412 38.413 43.588 199.720 1.00 17.05 A ATOM 2176 O ILE A 412 37.298 43.410 200.214 1.00 18.27 A ATOM 2177 N ASN A 413 38.780 44.714 199.113 1.00 17.73 A ATOM 2178 CA ASN A 413 37.869 45.830 198.891 1.00 17.76 A ATOM 2179 CB ASN A 413 38.570 47.173 199.155 1.00 19.37 A ATOM 2180 CG ASN A 413 37.665 48.384 198.906 1.00 21.20 A ATOM 2181 OD1 ASN A 413 37.098 48.549 197.828 1.00 21.10 A ATOM 2182 ND2 ASN A 413 37.573 49.257 199.893 1.00 21.56 A ATOM 2183 C ASN A 413 37.520 45.653 197.410 1.00 16.29 A ATOM 2184 O ASN A 413 38.367 45.845 196.532 1.00 14.73 A ATOM 2185 N TRP A 414 36.264 45.293 197.156 1.00 15.91 A ATOM 2186 CA TRP A 414 35.763 45.034 195.807 1.00 16.45 A ATOM 2187 CB TRP A 414 34.415 44.311 195.880 1.00 13.45 A ATOM 2188 CG TRP A 414 34.584 42.970 196.530 1.00 14.40 A ATOM 2189 CD2 TRP A 414 35.140 41.795 195.927 1.00 11.06 A ATOM 2190 CE2 TRP A 414 35.255 40.816 196.950 1.00 12.17 A ATOM 2191 CE3 TRP A 414 35.563 41.471 194.620 1.00 11.86 A ATOM 2192 CD1 TRP A 414 34.372 42.661 197.850 1.00 12.42 A ATOM 2193 NE1 TRP A 414 34.781 41.373 198.108 1.00 13.10 A ATOM 2194 CZ2 TRP A 414 35.781 39.527 196.709 1.00 11.22 A ATOM 2195 CZ3 TRP A 414 36.087 40.188 194.376 1.00 10.37 A ATOM 2196 CH2 TRP A 414 36.190 39.230 195.424 1.00 11.11 A ATOM 2197 C TRP A 414 35.751 46.181 194.812 1.00 17.39 A ATOM 2198 O TRP A 414 35.760 45.951 193.597 1.00 17.89 A ATOM 2199 N GLN A 415 35.782 47.409 195.326 1.00 18.71 A ATOM 2200 CA GLN A 415 35.829 48.590 194.473 1.00 20.74 A ATOM 2201 CB GLN A 415 35.189 49.804 195.152 1.00 24.69 A ATOM 2202 CG GLN A 415 33.661 49.752 195.198 1.00 29.88 A ATOM 2203 CD GLN A 415 33.001 49.730 193.817 1.00 34.21 A ATOM 2204 OE1 GLN A 415 33.336 50.527 192.935 1.00 37.63 A ATOM 2205 NE2 GLN A 415 32.051 48.816 193.633 1.00 35.32 A ATOM 2206 C GLN A 415 37.274 48.873 194.071 1.00 21.49 A ATOM 2207 O GLN A 415 37.524 49.369 192.975 1.00 22.13 A ATOM 2208 N ASP A 416 38.216 48.486 194.937 1.00 21.58 A ATOM 2209 CA ASP A 416 39.653 48.651 194.681 1.00 21.45 A ATOM 2210 CB ASP A 416 40.474 48.432 195.956 1.00 21.37 A ATOM 2211 CG ASP A 416 40.464 49.636 196.897 1.00 24.16 A ATOM 2212 OD1 ASP A 416 39.787 50.653 196.619 1.00 25.95 A ATOM 2213 OD2 ASP A 416 41.144 49.548 197.939 1.00 23.18 A ATOM 2214 C ASP A 416 40.115 47.647 193.621 1.00 21.58 A ATOM 2215 O ASP A 416 41.055 47.917 192.868 1.00 21.69 A ATOM 2216 N VAL A 417 39.430 46.500 193.571 1.00 20.41 A ATOM 2217 CA VAL A 417 39.720 45.429 192.614 1.00 19.94 A ATOM 2218 CB VAL A 417 38.987 44.101 192.996 1.00 19.93 A ATOM 2219 CG1 VAL A 417 39.178 43.016 191.926 1.00 17.42 A ATOM 2220 CG2 VAL A 417 39.528 43.584 194.297 1.00 17.75 A ATOM 2221 C VAL A 417 39.344 45.869 191.199 1.00 20.99 A ATOM 2222 O VAL A 417 40.213 45.922 190.334 1.00 21.45 A ATOM 2223 N VAL A 418 38.082 46.270 191.006 1.00 20.67 A ATOM 2224 CA VAL A 418 37.575 46.703 189.697 1.00 23.32 A ATOM 2225 CB VAL A 418 36.002 46.789 189.694 1.00 23.10 A ATOM 2226 CG1 VAL A 418 35.492 47.986 190.497 1.00 23.90 A ATOM 2227 CG2 VAL A 418 35.458 46.805 188.270 1.00 24.63 A ATOM 2228 C VAL A 418 38.234 47.988 189.154 1.00 23.66 A ATOM 2229 O VAL A 418 38.341 48.170 187.942 1.00 24.79 A ATOM 2230 N GLN A 419 38.717 48.839 190.058 1.00 24.64 A ATOM 2231 CA GLN A 419 39.381 50.087 189.677 1.00 26.12 A ATOM 2232 CB GLN A 419 39.044 51.203 190.678 1.00 27.13 A ATOM 2233 CG GLN A 419 37.590 51.677 190.619 1.00 29.70 A ATOM 2234 CD GLN A 419 37.243 52.666 191.720 1.00 31.46 A ATOM 2235 OE1 GLN A 419 36.443 52.370 192.607 1.00 32.13 A ATOM 2236 NE2 GLN A 419 37.837 53.853 191.660 1.00 31.64 A ATOM 2237 C GLN A 419 40.900 49.935 189.518 1.00 26.30 A ATOM 2238 O GLN A 419 41.603 50.924 189.285 1.00 25.43 A ATOM 2239 N LYS A 420 41.383 48.688 189.623 1.00 26.79 A ATOM 2240 CA LYS A 420 42.806 48.305 189.494 1.00 28.25 A ATOM 2241 CB LYS A 420 43.297 48.489 188.045 1.00 29.48 A ATOM 2242 CG LYS A 420 42.849 47.437 187.052 1.00 31.95 A ATOM 2243 CD LYS A 420 43.363 47.799 185.670 1.00 33.87 A ATOM 2244 CE LYS A 420 43.263 46.639 184.705 1.00 36.54 A ATOM 2245 NZ LYS A 420 43.670 47.044 183.331 1.00 37.53 A ATOM 2246 C LYS A 420 43.781 48.989 190.467 1.00 28.96 A ATOM 2247 O LYS A 420 44.945 49.226 190.128 1.00 29.26 A ATOM 2248 N LYS A 421 43.311 49.262 191.684 1.00 29.05 A ATOM 2249 CA LYS A 421 44.118 49.927 192.712 1.00 30.32 A ATOM 2250 CB LYS A 421 43.219 50.633 193.731 1.00 30.17 A ATOM 2251 CG LYS A 421 42.369 51.755 193.156 1.00 29.79 A ATOM 2252 CD LYS A 421 41.592 52.450 194.257 1.00 30.47 A ATOM 2253 CE LYS A 421 40.647 53.491 193.701 1.00 31.51 A ATOM 2254 NZ LYS A 421 39.903 54.178 194.792 1.00 31.93 A ATOM 2255 C LYS A 421 45.096 49.013 193.445 1.00 31.69 A ATOM 2256 O LYS A 421 46.060 49.493 194.050 1.00 33.59 A ATOM 2257 N LEU A 422 44.854 47.704 193.381 1.00 32.62 A ATOM 2258 CA LEU A 422 45.712 46.721 194.041 1.00 32.37 A ATOM 2259 CB LEU A 422 44.920 45.452 194.382 1.00 33.90 A ATOM 2260 CG LEU A 422 43.839 45.531 195.469 1.00 34.03 A ATOM 2261 CD1 LEU A 422 43.122 44.198 195.558 1.00 33.87 A ATOM 2262 CD2 LEU A 422 44.444 45.895 196.823 1.00 35.38 A ATOM 2263 C LEU A 422 46.958 46.372 193.232 1.00 31.85 A ATOM 2264 O LEU A 422 46.887 46.188 192.013 1.00 32.31 A ATOM 2265 N LEU A 423 48.094 46.313 193.929 1.00 30.37 A ATOM 2266 CA LEU A 423 49.399 45.998 193.340 1.00 29.21 A ATOM 2267 CB LEU A 423 50.524 46.430 194.304 1.00 30.06 A ATOM 2268 CG LEU A 423 52.018 46.171 194.021 1.00 31.99 A ATOM 2269 CD1 LEU A 423 52.507 46.964 192.813 1.00 31.88 A ATOM 2270 CD2 LEU A 423 52.837 46.539 195.250 1.00 31.74 A ATOM 2271 C LEU A 423 49.521 44.501 193.008 1.00 26.95 A ATOM 2272 O LEU A 423 49.266 43.656 193.871 1.00 27.20 A ATOM 2273 N PRO A 424 49.844 44.159 191.735 1.00 25.86 A ATOM 2274 CD PRO A 424 49.831 45.042 190.550 1.00 23.71 A ATOM 2275 CA PRO A 424 49.996 42.759 191.311 1.00 23.59 A ATOM 2276 CB PRO A 424 50.170 42.880 189.794 1.00 23.55 A ATOM 2277 CG PRO A 424 49.393 44.103 189.464 1.00 25.21 A ATOM 2278 C PRO A 424 51.201 42.057 191.958 1.00 22.61 A ATOM 2279 O PRO A 424 52.268 42.658 192.085 1.00 22.14 A ATOM 2280 N PRO A 425 51.032 40.792 192.412 1.00 21.49 A ATOM 2281 CD PRO A 425 49.751 40.070 192.518 1.00 22.31 A ATOM 2282 CA PRO A 425 52.097 40.005 193.047 1.00 21.27 A ATOM 2283 CB PRO A 425 51.326 38.855 193.696 1.00 20.79 A ATOM 2284 CG PRO A 425 50.179 38.658 192.775 1.00 19.95 A ATOM 2285 C PRO A 425 53.160 39.504 192.065 1.00 20.52 A ATOM 2286 O PRO A 425 54.187 38.959 192.473 1.00 20.46 A ATOM 2287 N PHE A 426 52.893 39.705 190.775 1.00 20.11 A ATOM 2288 CA PHE A 426 53.796 39.313 189.701 1.00 20.51 A ATOM 2289 CB PHE A 426 53.572 37.837 189.305 1.00 21.57 A ATOM 2290 CG PHE A 426 54.572 37.310 188.298 1.00 23.74 A ATOM 2291 CD1 PHE A 426 55.909 37.066 188.673 1.00 26.85 A ATOM 2292 CD2 PHE A 426 54.191 37.092 186.959 1.00 26.11 A ATOM 2293 CE1 PHE A 426 56.865 36.613 187.723 1.00 27.97 A ATOM 2294 CE2 PHE A 426 55.132 36.641 185.996 1.00 26.89 A ATOM 2295 CZ PHE A 426 56.474 36.401 186.380 1.00 27.49 A ATOM 2296 C PHE A 426 53.575 40.216 188.492 1.00 19.87 A ATOM 2297 O PHE A 426 52.450 40.350 188.003 1.00 19.07 A ATOM 2298 N LYS A 427 54.653 40.843 188.031 1.00 20.11 A ATOM 2299 CA LYS A 427 54.586 41.690 186.851 1.00 19.92 A ATOM 2300 CB LYS A 427 55.129 43.110 187.104 1.00 23.46 A ATOM 2301 CG LYS A 427 54.904 44.050 185.898 1.00 26.03 A ATOM 2302 CD LYS A 427 55.558 45.414 186.026 1.00 29.53 A ATOM 2303 CE LYS A 427 55.402 46.181 184.717 1.00 31.56 A ATOM 2304 NZ LYS A 427 55.924 47.576 184.777 1.00 33.40 A ATOM 2305 C LYS A 427 55.407 40.998 185.764 1.00 19.78 A ATOM 2306 O LYS A 427 56.554 40.613 186.005 1.00 17.85 A ATOM 2307 N PRO A 428 54.795 40.744 184.586 1.00 19.63 A ATOM 2308 CD PRO A 428 53.357 40.865 184.285 1.00 19.37 A ATOM 2309 CA PRO A 428 55.479 40.097 183.462 1.00 19.43 A ATOM 2310 CB PRO A 428 54.403 40.107 182.380 1.00 18.78 A ATOM 2311 CG PRO A 428 53.177 39.887 183.175 1.00 20.13 A ATOM 2312 C PRO A 428 56.708 40.902 183.039 1.00 19.52 A ATOM 2313 O PRO A 428 56.621 42.119 182.843 1.00 18.89 A ATOM 2314 N GLN A 429 57.852 40.223 182.988 1.00 20.38 A ATOM 2315 CA GLN A 429 59.130 40.841 182.632 1.00 23.68 A ATOM 2316 CB GLN A 429 60.277 40.166 183.405 1.00 24.40 A ATOM 2317 CG GLN A 429 60.268 40.410 184.915 1.00 28.23 A ATOM 2318 CD GLN A 429 60.626 41.840 185.292 1.00 29.68 A ATOM 2319 OE1 GLN A 429 61.800 42.209 185.331 1.00 33.85 A ATOM 2320 NE2 GLN A 429 59.611 42.648 185.582 1.00 31.72 A ATOM 2321 C GLN A 429 59.430 40.884 181.132 1.00 24.80 A ATOM 2322 O GLN A 429 60.529 40.532 180.692 1.00 24.99 A ATOM 2323 N VAL A 430 58.453 41.355 180.360 1.00 25.32 A ATOM 2324 CA VAL A 430 58.585 41.480 178.908 1.00 26.94 A ATOM 2325 CB VAL A 430 57.196 41.446 178.189 1.00 25.86 A ATOM 2326 CG1 VAL A 430 56.643 40.031 178.201 1.00 26.31 A ATOM 2327 CG2 VAL A 430 56.197 42.403 178.850 1.00 26.32 A ATOM 2328 C VAL A 430 59.374 42.739 178.526 1.00 28.11 A ATOM 2329 O VAL A 430 59.141 43.819 179.079 1.00 28.91 A ATOM 2330 N THR A 431 60.335 42.572 177.617 1.00 28.63 A ATOM 2331 CA THR A 431 61.196 43.664 177.151 1.00 30.71 A ATOM 2332 CB THR A 431 62.589 43.141 176.737 1.00 31.07 A ATOM 2333 OG1 THR A 431 62.442 42.057 175.811 1.00 32.95 A ATOM 2334 CG2 THR A 431 63.369 42.672 177.959 1.00 31.57 A ATOM 2335 C THR A 431 60.595 44.457 175.990 1.00 31.23 A ATOM 2336 O THR A 431 60.789 45.671 175.888 1.00 32.41 A ATOM 2337 N SER A 432 59.886 43.748 175.116 1.00 31.42 A ATOM 2338 CA SER A 432 59.227 44.338 173.954 1.00 31.65 A ATOM 2339 CB SER A 432 60.023 44.038 172.676 1.00 32.10 A ATOM 2340 OG SER A 432 60.171 42.643 172.462 1.00 30.64 A ATOM 2341 C SER A 432 57.816 43.765 173.844 1.00 31.86 A ATOM 2342 O SER A 432 57.450 42.851 174.587 1.00 31.28 A ATOM 2343 N GLU A 433 57.033 44.296 172.909 1.00 32.49 A ATOM 2344 CA GLU A 433 55.663 43.836 172.685 1.00 33.34 A ATOM 2345 CB GLU A 433 54.854 44.928 171.980 1.00 35.90 A ATOM 2346 CG GLU A 433 54.521 46.158 172.830 1.00 39.92 A ATOM 2347 CD GLU A 433 53.369 45.924 173.801 1.00 42.93 A ATOM 2348 OE1 GLU A 433 52.204 45.874 173.346 1.00 44.52 A ATOM 2349 OE2 GLU A 433 53.628 45.796 175.018 1.00 45.85 A ATOM 2350 C GLU A 433 55.618 42.526 171.884 1.00 32.35 A ATOM 2351 O GLU A 433 54.568 41.888 171.779 1.00 34.04 A ATOM 2352 N VAL A 434 56.776 42.126 171.357 1.00 29.34 A ATOM 2353 CA VAL A 434 56.923 40.902 170.570 1.00 27.57 A ATOM 2354 CB VAL A 434 57.732 41.198 169.247 1.00 28.24 A ATOM 2355 CG1 VAL A 434 59.233 41.366 169.516 1.00 27.69 A ATOM 2356 CG2 VAL A 434 57.455 40.146 168.184 1.00 29.67 A ATOM 2357 C VAL A 434 57.544 39.763 171.419 1.00 25.80 A ATOM 2358 O VAL A 434 57.710 38.635 170.947 1.00 26.50 A ATOM 2359 N ASP A 435 57.854 40.078 172.679 1.00 22.61 A ATOM 2360 CA ASP A 435 58.442 39.139 173.640 1.00 20.42 A ATOM 2361 CB ASP A 435 59.008 39.931 174.832 1.00 20.57 A ATOM 2362 CG ASP A 435 59.900 39.101 175.758 1.00 21.84 A ATOM 2363 OD1 ASP A 435 59.839 37.852 175.753 1.00 21.41 A ATOM 2364 OD2 ASP A 435 60.669 39.727 176.517 1.00 22.72 A ATOM 2365 C ASP A 435 57.355 38.156 174.103 1.00 19.53 A ATOM 2366 O ASP A 435 56.418 38.537 174.810 1.00 19.91 A ATOM 2367 N THR A 436 57.490 36.900 173.678 1.00 16.13 A ATOM 2368 CA THR A 436 56.529 35.845 174.009 1.00 14.69 A ATOM 2369 CB THR A 436 55.988 35.164 172.719 1.00 15.23 A ATOM 2370 OG1 THR A 436 57.083 34.673 171.934 1.00 17.12 A ATOM 2371 CG2 THR A 436 55.166 36.139 171.889 1.00 14.36 A ATOM 2372 C THR A 436 57.098 34.776 174.957 1.00 13.23 A ATOM 2373 O THR A 436 56.737 33.595 174.862 1.00 13.45 A ATOM 2374 N ARG A 437 57.940 35.204 175.903 1.00 11.51 A ATOM 2375 CA ARG A 437 58.581 34.301 176.872 1.00 12.26 A ATOM 2376 CB ARG A 437 59.638 35.049 177.696 1.00 13.67 A ATOM 2377 CG ARG A 437 59.081 36.111 178.628 1.00 13.51 A ATOM 2378 CD ARG A 437 60.154 36.732 179.486 1.00 15.66 A ATOM 2379 NE ARG A 437 60.964 37.681 178.733 1.00 17.26 A ATOM 2380 CZ ARG A 437 62.110 38.195 179.163 1.00 16.07 A ATOM 2381 NH1 ARG A 437 62.595 37.852 180.349 1.00 17.27 A ATOM 2382 NH2 ARG A 437 62.767 39.062 178.407 1.00 19.67 A ATOM 2383 C ARG A 437 57.606 33.579 177.813 1.00 11.96 A ATOM 2384 O ARG A 437 57.958 32.571 178.432 1.00 12.52 A ATOM 2385 N TYR A 438 56.385 34.102 177.901 1.00 12.10 A ATOM 2386 CA TYR A 438 55.362 33.520 178.760 1.00 10.77 A ATOM 2387 CB TYR A 438 54.675 34.607 179.583 1.00 11.18 A ATOM 2388 CG TYR A 438 55.614 35.336 180.515 1.00 11.04 A ATOM 2389 CD1 TYR A 438 55.794 36.724 180.407 1.00 12.49 A ATOM 2390 CE1 TYR A 438 56.690 37.408 181.254 1.00 14.41 A ATOM 2391 CD2 TYR A 438 56.352 34.638 181.500 1.00 13.83 A ATOM 2392 CE2 TYR A 438 57.250 35.318 182.364 1.00 12.87 A ATOM 2393 CZ TYR A 438 57.409 36.701 182.230 1.00 14.15 A ATOM 2394 OH TYR A 438 58.259 37.379 183.065 1.00 16.58 A ATOM 2395 C TYR A 438 54.359 32.630 178.038 1.00 10.95 A ATOM 2396 O TYR A 438 53.292 32.298 178.568 1.00 12.70 A ATOM 2397 N PHE A 439 54.726 32.251 176.819 1.00 11.45 A ATOM 2398 CA PHE A 439 53.935 31.359 175.983 1.00 12.49 A ATOM 2399 CB PHE A 439 53.525 32.055 174.684 1.00 11.92 A ATOM 2400 CG PHE A 439 52.465 33.099 174.873 1.00 11.02 A ATOM 2401 CD1 PHE A 439 52.814 34.431 175.176 1.00 9.95 A ATOM 2402 CD2 PHE A 439 51.105 32.752 174.779 1.00 10.65 A ATOM 2403 CE1 PHE A 439 51.820 35.417 175.386 1.00 8.73 A ATOM 2404 CE2 PHE A 439 50.090 33.727 174.987 1.00 11.34 A ATOM 2405 CZ PHE A 439 50.452 35.063 175.291 1.00 10.88 A ATOM 2406 C PHE A 439 54.799 30.137 175.703 1.00 13.60 A ATOM 2407 O PHE A 439 56.030 30.245 175.626 1.00 13.99 A ATOM 2408 N ASP A 440 54.157 28.974 175.595 1.00 16.16 A ATOM 2409 CA ASP A 440 54.857 27.708 175.349 1.00 19.82 A ATOM 2410 CB ASP A 440 53.894 26.524 175.465 1.00 22.10 A ATOM 2411 CG ASP A 440 53.392 26.317 176.875 1.00 27.42 A ATOM 2412 OD1 ASP A 440 52.186 26.540 177.109 1.00 30.82 A ATOM 2413 OD2 ASP A 440 54.201 25.935 177.750 1.00 30.42 A ATOM 2414 C ASP A 440 55.574 27.657 174.005 1.00 19.98 A ATOM 2415 O ASP A 440 55.037 28.118 172.993 1.00 19.33 A ATOM 2416 N ASP A 441 56.791 27.104 174.022 1.00 21.03 A ATOM 2417 CA ASP A 441 57.644 26.954 172.834 1.00 23.44 A ATOM 2418 CB ASP A 441 59.019 26.389 173.217 1.00 26.45 A ATOM 2419 CG ASP A 441 59.864 27.370 174.011 1.00 28.97 A ATOM 2420 OD1 ASP A 441 59.811 28.590 173.734 1.00 30.64 A ATOM 2421 OD2 ASP A 441 60.595 26.912 174.915 1.00 32.82 A ATOM 2422 C ASP A 441 57.011 26.056 171.774 1.00 22.99 A ATOM 2423 O ASP A 441 57.314 26.180 170.588 1.00 23.08 A ATOM 2424 N GLU A 442 56.095 25.194 172.222 1.00 21.93 A ATOM 2425 CA GLU A 442 55.349 24.258 171.374 1.00 24.14 A ATOM 2426 CB GLU A 442 54.434 23.394 172.259 1.00 27.03 A ATOM 2427 CG GLU A 442 53.712 22.238 171.555 1.00 32.34 A ATOM 2428 CD GLU A 442 52.816 21.443 172.493 1.00 35.35 A ATOM 2429 OE1 GLU A 442 51.940 22.046 173.154 1.00 35.80 A ATOM 2430 OE2 GLU A 442 52.989 20.207 172.567 1.00 38.32 A ATOM 2431 C GLU A 442 54.516 25.031 170.341 1.00 22.89 A ATOM 2432 O GLU A 442 54.305 24.557 169.222 1.00 23.30 A ATOM 2433 N PHE A 443 54.109 26.245 170.717 1.00 21.55 A ATOM 2434 CA PHE A 443 53.312 27.117 169.862 1.00 19.42 A ATOM 2435 CB PHE A 443 52.178 27.769 170.663 1.00 19.65 A ATOM 2436 CG PHE A 443 51.247 26.786 171.309 1.00 19.62 A ATOM 2437 CD1 PHE A 443 51.178 26.694 172.711 1.00 21.07 A ATOM 2438 CD2 PHE A 443 50.453 25.925 170.525 1.00 21.15 A ATOM 2439 CE1 PHE A 443 50.328 25.747 173.338 1.00 21.41 A ATOM 2440 CE2 PHE A 443 49.597 24.971 171.130 1.00 21.45 A ATOM 2441 CZ PHE A 443 49.535 24.881 172.540 1.00 22.37 A ATOM 2442 C PHE A 443 54.111 28.204 169.150 1.00 18.78 A ATOM 2443 O PHE A 443 53.990 28.352 167.938 1.00 19.73 A ATOM 2444 N THR A 444 54.945 28.933 169.896 1.00 18.79 A ATOM 2445 CA THR A 444 55.741 30.042 169.343 1.00 20.20 A ATOM 2446 CB THR A 444 56.357 30.926 170.449 1.00 18.90 A ATOM 2447 OG1 THR A 444 57.288 30.163 171.223 1.00 18.55 A ATOM 2448 CG2 THR A 444 55.269 31.479 171.354 1.00 18.16 A ATOM 2449 C THR A 444 56.830 29.696 168.329 1.00 21.39 A ATOM 2450 O THR A 444 57.235 30.556 167.542 1.00 22.19 A ATOM 2451 N ALA A 445 57.293 28.446 168.351 1.00 23.41 A ATOM 2452 CA ALA A 445 58.332 27.980 167.429 1.00 25.34 A ATOM 2453 CB ALA A 445 59.168 26.886 168.081 1.00 25.22 A ATOM 2454 C ALA A 445 57.761 27.493 166.095 1.00 27.29 A ATOM 2455 O ALA A 445 58.512 27.273 165.139 1.00 26.93 A ATOM 2456 N GLN A 446 56.434 27.351 166.034 1.00 28.39 A ATOM 2457 CA GLN A 446 55.735 26.898 164.829 1.00 30.40 A ATOM 2458 CB GLN A 446 54.319 26.422 165.164 1.00 31.32 A ATOM 2459 CG GLN A 446 54.240 25.068 165.848 1.00 32.45 A ATOM 2460 CD GLN A 446 52.807 24.610 166.067 1.00 33.93 A ATOM 2461 OE1 GLN A 446 52.348 24.488 167.203 1.00 34.49 A ATOM 2462 NE2 GLN A 446 52.090 24.361 164.975 1.00 34.58 A ATOM 2463 C GLN A 446 55.654 27.981 163.761 1.00 32.00 A ATOM 2464 O GLN A 446 55.357 29.140 164.059 1.00 31.38 A ATOM 2465 N SER A 447 55.934 27.590 162.519 1.00 34.38 A ATOM 2466 CA SER A 447 55.891 28.503 161.378 1.00 36.87 A ATOM 2467 CB SER A 447 56.785 27.989 160.242 1.00 37.47 A ATOM 2468 OG SER A 447 56.482 26.646 159.902 1.00 37.47 A ATOM 2469 C SER A 447 54.453 28.680 160.897 1.00 38.40 A ATOM 2470 O SER A 447 53.683 27.716 160.848 1.00 39.25 A ATOM 2471 N ILE A 448 54.090 29.927 160.604 1.00 40.49 A ATOM 2472 CA ILE A 448 52.749 30.274 160.131 1.00 42.86 A ATOM 2473 CB ILE A 448 52.111 31.412 160.988 1.00 42.99 A ATOM 2474 CG2 ILE A 448 51.539 30.826 162.281 1.00 43.72 A ATOM 2475 CG1 ILE A 448 53.133 32.524 161.278 1.00 42.57 A ATOM 2476 CD1 ILE A 448 52.548 33.770 161.891 1.00 42.57 A ATOM 2477 C ILE A 448 52.717 30.634 158.642 1.00 43.59 A ATOM 2478 O ILE A 448 53.473 31.497 158.181 1.00 44.55 A ATOM 2479 N ALA A 449 51.859 29.936 157.897 1.00 44.86 A ATOM 2480 CA ALA A 449 51.699 30.146 156.456 1.00 45.55 A ATOM 2481 CB ALA A 449 52.668 29.253 155.677 1.00 45.40 A ATOM 2482 C ALA A 449 50.263 29.874 156.017 1.00 46.17 A ATOM 2483 O ALA A 449 49.668 28.858 156.386 1.00 47.08 A ATOM 2484 N ALA A 466 26.345 36.321 148.790 1.00 55.65 A ATOM 2485 CA ALA A 466 26.716 36.093 150.182 1.00 55.32 A ATOM 2486 CB ALA A 466 26.650 37.403 150.968 1.00 55.16 A ATOM 2487 C ALA A 466 25.826 35.026 150.825 1.00 55.28 A ATOM 2488 O ALA A 466 24.699 35.306 151.250 1.00 55.63 A ATOM 2489 N ALA A 467 26.341 33.798 150.861 1.00 54.91 A ATOM 2490 CA ALA A 467 25.638 32.654 151.442 1.00 54.32 A ATOM 2491 CB ALA A 467 25.428 31.575 150.384 1.00 54.96 A ATOM 2492 C ALA A 467 26.403 32.088 152.638 1.00 53.99 A ATOM 2493 O ALA A 467 25.829 31.391 153.480 1.00 53.96 A ATOM 2494 N THR A 468 27.698 32.400 152.700 1.00 52.91 A ATOM 2495 CA THR A 468 28.586 31.953 153.777 1.00 51.02 A ATOM 2496 CB THR A 468 29.896 31.331 153.187 1.00 51.53 A ATOM 2497 OG1 THR A 468 30.720 30.827 154.246 1.00 52.59 A ATOM 2498 CG2 THR A 468 30.684 32.352 152.351 1.00 51.69 A ATOM 2499 C THR A 468 28.884 33.110 154.754 1.00 49.54 A ATOM 2500 O THR A 468 29.800 33.031 155.581 1.00 48.58 A ATOM 2501 N HIS A 469 28.068 34.163 154.663 1.00 48.00 A ATOM 2502 CA HIS A 469 28.188 35.363 155.495 1.00 46.23 A ATOM 2503 CB HIS A 469 27.474 36.541 154.810 1.00 46.08 A ATOM 2504 CG HIS A 469 27.777 37.879 155.412 1.00 45.97 A ATOM 2505 CD2 HIS A 469 27.023 38.708 156.174 1.00 45.86 A ATOM 2506 ND1 HIS A 469 28.988 38.515 155.238 1.00 46.38 A ATOM 2507 CE1 HIS A 469 28.966 39.677 155.866 1.00 46.15 A ATOM 2508 NE2 HIS A 469 27.786 39.818 156.442 1.00 46.02 A ATOM 2509 C HIS A 469 27.625 35.146 156.903 1.00 45.32 A ATOM 2510 O HIS A 469 26.439 34.841 157.074 1.00 45.07 A ATOM 2511 N PHE A 470 28.491 35.327 157.899 1.00 44.14 A ATOM 2512 CA PHE A 470 28.132 35.177 159.310 1.00 43.02 A ATOM 2513 CB PHE A 470 29.369 34.797 160.134 1.00 41.68 A ATOM 2514 CG PHE A 470 29.591 33.315 160.263 1.00 40.48 A ATOM 2515 CD1 PHE A 470 29.477 32.688 161.519 1.00 39.62 A ATOM 2516 CD2 PHE A 470 29.937 32.535 159.141 1.00 40.21 A ATOM 2517 CE1 PHE A 470 29.708 31.293 161.665 1.00 39.55 A ATOM 2518 CE2 PHE A 470 30.171 31.139 159.266 1.00 39.57 A ATOM 2519 CZ PHE A 470 30.057 30.517 160.533 1.00 39.80 A ATOM 2520 C PHE A 470 27.510 36.462 159.867 1.00 43.39 A ATOM 2521 O PHE A 470 28.119 37.536 159.773 1.00 42.56 A ATOM 2522 N PRO A 471 26.281 36.375 160.428 1.00 44.34 A ATOM 2523 CD PRO A 471 25.366 35.213 160.446 1.00 45.04 A ATOM 2524 CA PRO A 471 25.615 37.559 160.988 1.00 45.42 A ATOM 2525 CB PRO A 471 24.175 37.083 161.177 1.00 45.46 A ATOM 2526 CG PRO A 471 24.333 35.622 161.467 1.00 45.63 A ATOM 2527 C PRO A 471 26.223 38.074 162.295 1.00 46.03 A ATOM 2528 O PRO A 471 26.943 37.349 162.993 1.00 46.15 A ATOM 2529 N GLN A 472 25.926 39.340 162.590 1.00 46.33 A ATOM 2530 CA GLN A 472 26.381 40.069 163.781 1.00 46.54 A ATOM 2531 CB GLN A 472 25.639 39.600 165.042 1.00 47.23 A ATOM 2532 CG GLN A 472 24.141 39.861 164.977 1.00 49.30 A ATOM 2533 CD GLN A 472 23.496 39.887 166.336 1.00 50.05 A ATOM 2534 OE1 GLN A 472 23.577 40.886 167.050 1.00 50.50 A ATOM 2535 NE2 GLN A 472 22.851 38.787 166.709 1.00 50.49 A ATOM 2536 C GLN A 472 27.896 40.181 164.002 1.00 45.51 A ATOM 2537 O GLN A 472 28.380 40.245 165.136 1.00 45.91 A ATOM 2538 N PHE A 473 28.630 40.205 162.890 1.00 44.75 A ATOM 2539 CA PHE A 473 30.086 40.364 162.890 1.00 43.02 A ATOM 2540 CB PHE A 473 30.744 39.336 161.957 1.00 41.34 A ATOM 2541 CG PHE A 473 31.470 38.232 162.679 1.00 39.89 A ATOM 2542 CD1 PHE A 473 30.765 37.134 163.211 1.00 38.04 A ATOM 2543 CD2 PHE A 473 32.869 38.275 162.822 1.00 38.61 A ATOM 2544 CE1 PHE A 473 31.446 36.077 163.883 1.00 37.36 A ATOM 2545 CE2 PHE A 473 33.572 37.230 163.490 1.00 37.42 A ATOM 2546 CZ PHE A 473 32.854 36.127 164.022 1.00 37.19 A ATOM 2547 C PHE A 473 30.343 41.802 162.411 1.00 43.73 A ATOM 2548 O PHE A 473 29.480 42.671 162.602 1.00 45.51 A ATOM 2549 N ASP A 474 31.504 42.050 161.794 1.00 42.35 A ATOM 2550 CA ASP A 474 31.906 43.371 161.268 1.00 42.24 A ATOM 2551 CB ASP A 474 31.165 43.685 159.955 1.00 45.28 A ATOM 2552 CG ASP A 474 31.574 42.757 158.813 1.00 47.74 A ATOM 2553 OD1 ASP A 474 31.190 41.565 158.835 1.00 48.55 A ATOM 2554 OD2 ASP A 474 32.282 43.223 157.891 1.00 49.47 A ATOM 2555 C ASP A 474 31.819 44.527 162.288 1.00 40.00 A ATOM 2556 O ASP A 474 30.980 45.429 162.177 1.00 40.94 A ATOM 2557 N TYR A 475 32.704 44.465 163.282 1.00 36.44 A ATOM 2558 CA TYR A 475 32.779 45.442 164.370 1.00 33.09 A ATOM 2559 CB TYR A 475 32.573 44.700 165.706 1.00 30.04 A ATOM 2560 CG TYR A 475 32.771 45.478 167.006 1.00 24.95 A ATOM 2561 CD1 TYR A 475 31.737 46.274 167.546 1.00 23.36 A ATOM 2562 CE1 TYR A 475 31.896 46.933 168.802 1.00 22.57 A ATOM 2563 CD2 TYR A 475 33.973 45.359 167.741 1.00 22.85 A ATOM 2564 CE2 TYR A 475 34.144 46.011 168.993 1.00 21.48 A ATOM 2565 CZ TYR A 475 33.104 46.791 169.514 1.00 20.48 A ATOM 2566 OH TYR A 475 33.272 47.411 170.729 1.00 22.52 A ATOM 2567 C TYR A 475 34.101 46.216 164.380 1.00 33.06 A ATOM 2568 O TYR A 475 35.139 45.712 163.949 1.00 32.18 A ATOM 2569 N SER A 476 34.032 47.430 164.927 1.00 32.88 A ATOM 2570 CA SER A 476 35.161 48.347 165.087 1.00 34.71 A ATOM 2571 CB SER A 476 35.261 49.314 163.898 1.00 34.88 A ATOM 2572 OG SER A 476 35.573 48.628 162.695 1.00 34.52 A ATOM 2573 C SER A 476 34.898 49.124 166.376 1.00 35.91 A ATOM 2574 O SER A 476 33.831 49.729 166.532 1.00 36.10 A ATOM 2575 N ALA A 477 35.857 49.078 167.302 1.00 37.38 A ATOM 2576 CA ALA A 477 35.745 49.754 168.599 1.00 40.37 A ATOM 2577 CB ALA A 477 36.753 49.175 169.586 1.00 39.82 A ATOM 2578 C ALA A 477 35.883 51.271 168.536 1.00 42.21 A ATOM 2579 O ALA A 477 36.699 51.802 167.777 1.00 42.18 A ATOM 2580 N SER A 478 35.063 51.947 169.340 1.00 45.14 A ATOM 2581 CA SER A 478 35.035 53.407 169.431 1.00 47.33 A ATOM 2582 CB SER A 478 33.630 53.885 169.813 1.00 49.73 A ATOM 2583 OG SER A 478 32.676 53.498 168.837 1.00 50.82 A ATOM 2584 C SER A 478 36.063 53.955 170.424 1.00 48.10 A ATOM 2585 O SER A 478 36.592 55.053 170.228 1.00 47.74 A ATOM 2586 N ALA A 479 36.342 53.180 171.475 1.00 48.79 A ATOM 2587 CA ALA A 479 37.302 53.556 172.517 1.00 50.13 A ATOM 2588 CB ALA A 479 36.887 52.957 173.857 1.00 50.04 A ATOM 2589 C ALA A 479 38.724 53.124 172.160 1.00 50.67 A ATOM 2590 O ALA A 479 39.673 53.902 172.284 1.00 51.60 A ATOM 2591 PG ANP A 500 39.417 25.847 173.896 1.00 9.41 A ATOM 2592 N3B ANP A 500 40.344 26.913 173.019 1.00 10.38 A ATOM 2593 O1G ANP A 500 37.969 26.073 173.474 1.00 9.65 A ATOM 2594 O2G ANP A 500 39.744 26.245 175.274 1.00 8.04 A ATOM 2595 O3G ANP A 500 39.850 24.489 173.609 1.00 10.48 A ATOM 2596 PB ANP A 500 39.861 27.891 171.746 1.00 11.17 A ATOM 2597 O1B ANP A 500 39.952 27.125 170.525 1.00 13.09 A ATOM 2598 O2B ANP A 500 38.541 28.477 172.062 1.00 12.20 A ATOM 2599 PA ANP A 500 41.239 30.219 172.776 1.00 9.68 A ATOM 2600 O1A ANP A 500 40.479 31.439 172.504 1.00 9.02 A ATOM 2601 O2A ANP A 500 41.174 29.615 174.136 1.00 7.76 A ATOM 2602 O3A ANP A 500 40.938 29.083 171.660 1.00 11.08 A ATOM 2603 O5* ANP A 500 42.774 30.527 172.425 1.00 8.07 A ATOM 2604 C5* ANP A 500 43.761 29.488 172.580 1.00 9.46 A ATOM 2605 C4* ANP A 500 44.980 30.030 173.294 1.00 9.67 A ATOM 2606 O4* ANP A 500 45.424 31.254 172.662 1.00 11.95 A ATOM 2607 C3* ANP A 500 44.701 30.400 174.743 1.00 10.39 A ATOM 2608 O3* ANP A 500 44.708 29.285 175.636 1.00 10.49 A ATOM 2609 C2* ANP A 500 45.759 31.445 174.994 1.00 10.98 A ATOM 2610 O2* ANP A 500 47.007 30.817 175.342 1.00 10.67 A ATOM 2611 C1* ANP A 500 45.905 32.171 173.663 1.00 9.49 A ATOM 2612 N9 ANP A 500 45.115 33.414 173.660 1.00 10.60 A ATOM 2613 C8 ANP A 500 43.752 33.584 173.478 1.00 10.97 A ATOM 2614 N7 ANP A 500 43.357 34.811 173.540 1.00 11.38 A ATOM 2615 C5 ANP A 500 44.524 35.523 173.778 1.00 12.24 A ATOM 2616 C6 ANP A 500 44.777 36.902 173.952 1.00 11.76 A ATOM 2617 N6 ANP A 500 43.802 37.813 173.903 1.00 11.24 A ATOM 2618 N1 ANP A 500 46.084 37.297 174.178 1.00 13.39 A ATOM 2619 C2 ANP A 500 47.059 36.370 174.224 1.00 12.04 A ATOM 2620 N3 ANP A 500 46.929 35.038 174.075 1.00 10.58 A ATOM 2621 C4 ANP A 500 45.610 34.683 173.851 1.00 10.86 A ATOM 2622 MN MN A 501 40.473 28.238 175.472 1.00 9.43 A ATOM 2623 MN MN A 502 37.013 28.007 173.523 1.00 11.07 A ATOM 2624 C GLY B 3 50.740 18.235 185.265 1.00 34.68 B ATOM 2625 O GLY B 3 50.818 19.442 185.025 1.00 37.14 B ATOM 2626 N GLY B 3 51.802 17.798 187.495 1.00 36.33 B ATOM 2627 CA GLY B 3 51.851 17.538 186.029 1.00 35.97 B ATOM 2628 N ARG B 4 49.716 17.461 184.886 1.00 32.14 B ATOM 2629 CA ARG B 4 48.527 17.908 184.134 1.00 26.40 B ATOM 2630 CB ARG B 4 47.671 18.879 184.976 1.00 26.58 B ATOM 2631 CG ARG B 4 46.437 19.516 184.310 1.00 24.76 B ATOM 2632 CD ARG B 4 46.316 20.936 184.844 1.00 23.33 B ATOM 2633 NE ARG B 4 45.172 21.756 184.419 1.00 19.93 B ATOM 2634 CZ ARG B 4 44.915 22.175 183.179 1.00 18.01 B ATOM 2635 NH1 ARG B 4 45.685 21.832 182.155 1.00 14.82 B ATOM 2636 NH2 ARG B 4 43.992 23.104 182.990 1.00 18.10 B ATOM 2637 C ARG B 4 48.797 18.478 182.730 1.00 24.18 B ATOM 2638 O ARG B 4 49.389 19.557 182.591 1.00 22.33 B ATOM 2639 N PRO B 5 48.387 17.742 181.670 1.00 21.51 B ATOM 2640 CD PRO B 5 47.890 16.348 181.678 1.00 22.02 B ATOM 2641 CA PRO B 5 48.591 18.212 180.293 1.00 18.98 B ATOM 2642 CB PRO B 5 48.413 16.933 179.469 1.00 20.54 B ATOM 2643 CG PRO B 5 47.409 16.153 180.256 1.00 21.49 B ATOM 2644 C PRO B 5 47.553 19.275 179.913 1.00 18.20 B ATOM 2645 O PRO B 5 46.621 19.539 180.687 1.00 14.64 B ATOM 2646 N ARG B 6 47.716 19.865 178.727 1.00 17.95 B ATOM 2647 CA ARG B 6 46.792 20.883 178.214 1.00 17.65 B ATOM 2648 CB ARG B 6 47.255 21.430 176.868 1.00 20.26 B ATOM 2649 CG ARG B 6 48.392 22.398 176.947 1.00 23.07 B ATOM 2650 CD ARG B 6 48.511 23.194 175.656 1.00 22.64 B ATOM 2651 NE ARG B 6 47.416 24.148 175.441 1.00 22.34 B ATOM 2652 CZ ARG B 6 47.322 25.350 176.016 1.00 19.82 B ATOM 2653 NH1 ARG B 6 48.251 25.771 176.865 1.00 18.72 B ATOM 2654 NH2 ARG B 6 46.307 26.148 175.720 1.00 19.88 B ATOM 2655 C ARG B 6 45.403 20.299 178.036 1.00 16.97 B ATOM 2656 O ARG B 6 45.254 19.164 177.581 1.00 15.89 B ATOM 2657 N THR B 7 44.396 21.072 178.431 1.00 15.56 B ATOM 2658 CA THR B 7 43.010 20.635 178.336 1.00 17.45 B ATOM 2659 CB THR B 7 42.294 20.722 179.713 1.00 17.68 B ATOM 2660 OG1 THR B 7 42.156 22.093 180.107 1.00 21.53 B ATOM 2661 CG2 THR B 7 43.057 19.973 180.789 1.00 18.88 B ATOM 2662 C THR B 7 42.253 21.468 177.303 1.00 17.25 B ATOM 2663 O THR B 7 42.388 22.697 177.268 1.00 19.69 B ATOM 2664 N THR B 8 41.481 20.791 176.454 1.00 16.02 B ATOM 2665 CA THR B 8 40.697 21.455 175.409 1.00 15.55 B ATOM 2666 CB THR B 8 41.025 20.895 173.996 1.00 18.90 B ATOM 2667 OG1 THR B 8 40.925 19.465 174.006 1.00 21.52 B ATOM 2668 CG2 THR B 8 42.426 21.303 173.560 1.00 21.36 B ATOM 2669 C THR B 8 39.198 21.324 175.671 1.00 13.80 B ATOM 2670 O THR B 8 38.754 20.392 176.349 1.00 13.33 B ATOM 2671 N SER B 9 38.422 22.260 175.129 1.00 12.68 B ATOM 2672 CA SER B 9 36.973 22.249 175.307 1.00 12.47 B ATOM 2673 CB SER B 9 36.405 23.674 175.249 1.00 14.21 B ATOM 2674 OG SER B 9 36.285 24.142 173.911 1.00 14.37 B ATOM 2675 C SER B 9 36.245 21.361 174.296 1.00 12.76 B ATOM 2676 O SER B 9 36.841 20.887 173.323 1.00 14.55 B ATOM 2677 N PHE B 10 34.962 21.126 174.561 1.00 13.76 B ATOM 2678 CA PHE B 10 34.100 20.333 173.688 1.00 13.46 B ATOM 2679 CB PHE B 10 34.083 18.836 174.100 1.00 16.28 B ATOM 2680 CG PHE B 10 33.284 18.538 175.355 1.00 14.94 B ATOM 2681 CD1 PHE B 10 31.961 18.045 175.265 1.00 16.82 B ATOM 2682 CD2 PHE B 10 33.828 18.789 176.625 1.00 17.22 B ATOM 2683 CE1 PHE B 10 31.186 17.816 176.429 1.00 15.52 B ATOM 2684 CE2 PHE B 10 33.067 18.564 177.805 1.00 14.78 B ATOM 2685 CZ PHE B 10 31.741 18.078 177.702 1.00 15.44 B ATOM 2686 C PHE B 10 32.693 20.926 173.732 1.00 13.91 B ATOM 2687 O PHE B 10 32.360 21.692 174.642 1.00 11.85 B ATOM 2688 N ALA B 11 31.867 20.510 172.776 1.00 14.09 B ATOM 2689 CA ALA B 11 30.476 20.930 172.671 1.00 16.39 B ATOM 2690 CB ALA B 11 30.357 22.277 171.951 1.00 15.47 B ATOM 2691 C ALA B 11 29.748 19.839 171.899 1.00 19.04 B ATOM 2692 O ALA B 11 30.139 19.501 170.776 1.00 19.18 B ATOM 2693 N GLU B 12 28.740 19.248 172.542 1.00 21.65 B ATOM 2694 CA GLU B 12 27.927 18.180 171.951 1.00 26.02 B ATOM 2695 CB GLU B 12 27.165 17.433 173.055 1.00 28.33 B ATOM 2696 CG GLU B 12 26.435 16.157 172.618 1.00 32.22 B ATOM 2697 CD GLU B 12 25.643 15.520 173.751 1.00 34.95 B ATOM 2698 OE1 GLU B 12 24.628 16.115 174.182 1.00 36.56 B ATOM 2699 OE2 GLU B 12 26.036 14.425 174.211 1.00 36.85 B ATOM 2700 C GLU B 12 26.948 18.750 170.917 1.00 27.72 B ATOM 2701 O GLU B 12 26.264 19.748 171.238 1.00 27.95 B ATOM 2702 OXT GLU B 12 26.890 18.194 169.798 1.00 29.77 B ATOM 2703 OH2 TIP S 1 35.513 19.462 187.609 1.00 8.68 S ATOM 2704 OH2 TIP S 2 34.119 23.788 181.779 1.00 8.79 S ATOM 2705 OH2 TIP S 3 50.965 30.957 178.095 1.00 11.42 S ATOM 2706 OH2 TIP S 4 39.194 18.375 188.406 1.00 7.91 S ATOM 2707 OH2 TIP S 5 33.495 30.603 176.993 1.00 12.70 S ATOM 2708 OH2 TIP S 6 33.279 17.866 195.059 1.00 11.14 S ATOM 2709 OH2 TIP S 7 49.067 29.203 174.198 1.00 16.63 S ATOM 2710 OH2 TIP S 8 30.715 23.037 184.039 1.00 14.80 S ATOM 2711 OH2 TIP S 9 46.349 17.630 188.194 1.00 15.87 S ATOM 2712 OH2 TIP S 10 22.572 18.305 190.665 1.00 16.99 S ATOM 2713 OH2 TIP S 11 36.637 44.504 178.296 1.00 10.61 S ATOM 2714 OH2 TIP S 12 20.954 30.509 186.356 1.00 13.91 S ATOM 2715 OH2 TIP S 13 35.546 27.646 175.192 1.00 15.04 S ATOM 2716 OH2 TIP S 14 50.275 38.942 188.553 1.00 13.53 S ATOM 2717 OH2 TIP S 15 35.330 42.723 176.495 1.00 13.11 S ATOM 2718 OH2 TIP S 16 55.177 36.700 176.903 1.00 11.19 S ATOM 2719 OH2 TIP S 17 55.266 31.109 165.695 1.00 18.50 S ATOM 2720 OH2 TIP S 18 41.312 16.013 203.045 1.00 20.46 S ATOM 2721 OH2 TIP S 19 50.201 30.584 201.352 1.00 16.58 S ATOM 2722 OH2 TIP S 20 36.996 34.711 172.597 1.00 15.08 S ATOM 2723 OH2 TIP S 21 29.676 18.119 197.893 1.00 13.47 S ATOM 2724 OH2 TIP S 22 40.919 15.924 195.875 1.00 15.77 S ATOM 2725 OH2 TIP S 23 23.000 12.106 190.288 1.00 14.25 S ATOM 2726 OH2 TIP S 24 52.949 32.525 194.744 1.00 13.76 S ATOM 2727 OH2 TIP S 25 33.009 27.747 184.065 1.00 15.77 S ATOM 2728 OH2 TIP S 26 22.253 26.995 191.698 1.00 16.31 S ATOM 2729 OH2 TIP S 27 58.929 31.921 183.099 1.00 17.72 S ATOM 2730 OH2 TIP S 28 22.864 38.421 177.895 1.00 13.50 S ATOM 2731 OH2 TIP S 29 48.171 19.107 197.167 1.00 17.80 S ATOM 2732 OH2 TIP S 30 23.481 32.542 173.772 1.00 17.19 S ATOM 2733 OH2 TIP S 31 59.971 25.389 187.105 1.00 14.41 S ATOM 2734 OH2 TIP S 32 36.493 24.796 181.760 1.00 13.84 S ATOM 2735 OH2 TIP S 33 35.916 29.549 169.844 1.00 19.69 S ATOM 2736 OH2 TIP S 34 26.760 18.671 197.567 1.00 13.32 S ATOM 2737 OH2 TIP S 35 51.205 29.093 176.132 1.00 11.39 S ATOM 2738 OH2 TIP S 36 35.408 41.548 201.022 1.00 14.63 S ATOM 2739 OH2 TIP S 37 48.677 43.513 177.997 1.00 22.26 S ATOM 2740 OH2 TIP S 38 55.545 26.769 182.425 1.00 20.34 S ATOM 2741 OH2 TIP S 39 51.976 46.164 187.557 1.00 20.17 S ATOM 2742 OH2 TIP S 40 47.037 22.259 187.710 1.00 20.21 S ATOM 2743 OH2 TIP S 41 34.633 38.852 202.253 1.00 14.95 S ATOM 2744 OH2 TIP S 42 30.505 23.971 181.497 1.00 14.52 S ATOM 2745 OH2 TIP S 43 40.037 34.151 172.734 1.00 15.01 S ATOM 2746 OH2 TIP S 44 24.388 25.120 188.049 1.00 20.05 S ATOM 2747 OH2 TIP S 45 32.659 32.730 205.273 1.00 18.75 S ATOM 2748 OH2 TIP S 46 59.518 32.651 180.652 1.00 19.23 S ATOM 2749 OH2 TIP S 47 20.673 26.102 176.394 1.00 15.77 S ATOM 2750 OH2 TIP S 48 26.440 26.553 168.049 1.00 18.31 S ATOM 2751 OH2 TIP S 49 25.405 15.362 191.412 1.00 18.80 S ATOM 2752 OH2 TIP S 50 35.319 44.324 174.147 1.00 19.55 S ATOM 2753 OH2 TIP S 51 55.207 40.912 175.135 1.00 20.88 S ATOM 2754 OH2 TIP S 52 56.981 40.770 189.703 1.00 18.54 S ATOM 2755 OH2 TIP S 53 48.076 23.195 189.959 1.00 19.55 S ATOM 2756 OH2 TIP S 54 48.774 27.766 198.643 1.00 14.67 S ATOM 2757 OH2 TIP S 55 32.106 43.138 189.021 1.00 22.66 S ATOM 2758 OH2 TIP S 56 24.074 39.850 175.826 1.00 28.15 S ATOM 2759 OH2 TIP S 57 21.973 33.790 197.949 1.00 34.40 S ATOM 2760 OH2 TIP S 58 22.026 24.203 188.263 1.00 21.34 S ATOM 2761 OH2 TIP S 59 33.453 16.616 197.704 1.00 23.05 S ATOM 2762 OH2 TIP S 60 50.801 27.570 178.959 1.00 28.34 S ATOM 2763 OH2 TIP S 61 52.902 39.224 157.977 1.00 23.75 S ATOM 2764 OH2 TIP S 62 41.488 7.599 189.155 1.00 19.38 S ATOM 2765 OH2 TIP S 63 38.845 11.799 201.454 1.00 27.38 S ATOM 2766 OH2 TIP S 64 19.536 28.443 177.717 1.00 18.22 S ATOM 2767 OH2 TIP S 65 28.303 12.355 195.234 1.00 22.19 S ATOM 2768 OH2 TIP S 66 21.973 18.597 178.917 1.00 25.36 S ATOM 2769 OH2 TIP S 67 37.673 25.400 207.417 1.00 21.23 S ATOM 2770 OH2 TIP S 68 25.125 17.966 191.418 1.00 22.23 S ATOM 2771 OH2 TIP S 69 41.253 13.685 181.348 1.00 22.30 S ATOM 2772 OH2 TIP S 70 35.350 46.611 172.452 1.00 22.34 S ATOM 2773 OH2 TIP S 71 28.913 47.422 180.499 1.00 21.84 S ATOM 2774 OH2 TIP S 72 43.694 40.374 176.847 1.00 16.46 S ATOM 2775 OH2 TIP S 73 22.932 35.810 185.514 1.00 25.69 S ATOM 2776 OH2 TIP S 74 27.757 11.435 183.289 1.00 28.99 S ATOM 2777 OH2 TIP S 75 14.735 36.062 184.933 1.00 22.70 S ATOM 2778 OH2 TIP S 76 46.773 44.790 172.601 1.00 25.80 S ATOM 2779 OH2 TIP S 77 41.994 12.598 191.334 1.00 18.04 S ATOM 2780 OH2 TIP S 78 45.286 8.859 184.781 1.00 22.73 S ATOM 2781 OH2 TIP S 79 34.459 45.849 199.248 1.00 23.78 S ATOM 2782 OH2 TIP S 80 49.997 33.952 201.347 1.00 23.16 S ATOM 2783 OH2 TIP S 81 47.050 26.998 172.932 1.00 26.45 S ATOM 2784 OH2 TIP S 82 50.437 19.716 177.733 1.00 27.06 S ATOM 2785 OH2 TIP S 83 34.063 47.953 197.860 1.00 23.39 S ATOM 2786 OH2 TIP S 84 44.020 15.103 191.224 1.00 18.68 S ATOM 2787 OH2 TIP S 85 33.015 24.574 184.481 1.00 25.62 S ATOM 2788 OH2 TIP S 86 17.099 25.296 179.596 1.00 36.31 S ATOM 2789 OH2 TIP S 87 28.989 34.198 201.808 1.00 24.10 S ATOM 2790 OH2 TIP S 88 19.471 20.951 197.413 1.00 26.73 S ATOM 2791 OH2 TIP S 89 33.503 19.254 170.465 1.00 21.21 S ATOM 2792 OH2 TIP S 90 14.410 32.374 188.444 1.00 35.55 S ATOM 2793 OH2 TIP S 91 50.036 19.368 189.222 1.00 19.75 S ATOM 2794 OH2 TIP S 92 19.777 20.806 193.508 1.00 29.16 S ATOM 2795 OH2 TIP S 93 42.821 5.486 183.252 1.00 29.85 S ATOM 2854 OH2 TIP S 153 59.037 25.695 190.823 1.00 23.41 S ATOM 2855 OH2 TIP S 154 32.478 25.593 203.042 1.00 25.66 S ATOM 2856 OH2 TIP S 155 45.821 42.754 177.669 1.00 34.32 S ATOM 2857 OH2 TIP S 156 28.989 44.834 187.660 1.00 38.53 S ATOM 2858 OH2 TIP S 157 60.167 36.196 172.532 1.00 29.39 S ATOM 2859 OH2 TIP S 158 50.004 40.728 155.773 1.00 34.95 S ATOM 2860 OH2 TIP S 159 58.989 35.289 189.746 1.00 44.53 S ATOM 2861 OH2 TIP S 160 16.930 32.266 179.235 1.00 26.96 S ATOM 2862 OH2 TIP S 161 37.722 17.742 175.393 1.00 33.58 S ATOM 2863 OH2 TIP S 162 37.001 27.551 156.174 1.00 34.38 S ATOM 2864 OH2 TIP S 163 56.216 22.358 168.570 1.00 52.08 S ATOM 2865 OH2 TIP S 164 43.307 24.924 175.719 1.00 30.97 S ATOM 2866 OH2 TIP S 165 31.555 50.258 162.429 1.00 40.07 S ATOM 2867 OH2 TIP S 166 62.303 47.418 173.584 1.00 45.59 S ATOM 2868 OH2 TIP S 167 47.109 17.914 210.912 1.00 42.78 S ATOM 2869 OH2 TIP S 168 23.879 33.048 168.898 1.00 34.23 S ATOM 2870 OH2 TIP S 169 40.895 34.331 154.310 1.00 34.53 S ATOM 2871 OH2 TIP S 170 31.937 50.261 170.310 1.00 40.40 S ATOM 2872 OH2 TIP S 171 32.516 26.022 169.042 1.00 25.90 S ATOM 2873 OH2 TIP S 172 51.018 47.685 171.259 1.00 32.99 S ATOM 2874 OH2 TIP S 173 50.051 54.453 167.264 1.00 46.29 S ATOM 2875 OH2 TIP S 174 58.984 45.818 186.069 1.00 38.72 S ATOM 2876 OH2 TIP S 175 58.195 26.946 176.789 1.00 32.90 S ATOM 2877 OH2 TIP S 176 52.285 20.827 191.417 1.00 41.48 S ATOM 2878 OH2 TIP S 177 32.590 29.707 169.779 1.00 26.14 S ATOM 2879 OH2 TIP S 178 36.480 19.235 153.519 1.00 41.40 S ATOM 2880 OH2 TIP S 179 43.010 44.995 190.927 1.00 44.14 S ATOM 2881 OH2 TIP S 180 44.742 21.757 166.449 1.00 49.28 S ATOM 2882 OH2 TIP S 181 42.091 4.325 185.720 1.00 35.81 S ATOM 2883 OH2 TIP S 182 43.744 24.461 165.023 1.00 37.22 S ATOM 2884 OH2 TIP S 183 23.778 20.893 171.557 1.00 50.83 S ATOM 2885 OH2 TIP S 184 47.952 45.789 196.708 1.00 38.69 S ATOM 2886 OH2 TIP S 185 32.513 3.008 181.727 1.00 41.23 S ATOM 2887 OH2 TIP S 186 17.997 41.636 181.572 1.00 44.78 S ATOM 2888 OH2 TIP S 187 40.259 35.881 206.400 1.00 37.81 S ATOM 2889 OH2 TIP S 188 65.479 40.015 178.254 1.00 32.75 S ATOM 2890 OH2 TIP S 189 49.440 16.871 189.100 1.00 33.81 S ATOM 2891 OH2 TIP S 190 44.412 41.390 200.479 1.00 35.02 S ATOM 2892 OH2 TIP S 191 47.677 33.628 158.523 1.00 41.63 S ATOM 2893 OH2 TIP S 192 44.004 13.331 193.278 1.00 37.83 S ATOM 2894 OH2 TIP S 193 34.579 44.061 191.774 1.00 25.71 S ATOM 2895 OH2 TIP S 194 35.914 3.269 188.382 1.00 36.75 S ATOM 2896 OH2 TIP S 195 45.275 23.850 173.309 1.00 35.54 S ATOM 2897 OH2 TIP S 196 59.521 32.119 167.352 1.00 44.76 S ATOM 2898 OH2 TIP 210 42.509 27.406 175.671 1.00 7.70 ATOM 2899 OH2 TIP 213 35.527 27.997 171.928 1.00 12.93 ATOM 2900 OH2 TIP S 197 25.667 16.315 196.524 1.00 14.31 S ATOM 2901 OH2 TIP S 198 20.985 20.487 189.856 1.00 19.24 S ATOM 2902 OH2 TIP S 199 47.877 19.863 187.919 1.00 37.55 S ATOM 2903 OH2 TIP S 200 33.409 40.577 203.909 1.00 21.10 S ATOM 2904 OH2 TIP S 201 51.083 24.139 177.423 1.00 29.24 S ATOM 2905 OH2 TIP S 202 40.108 12.526 193.310 1.00 24.57 S ATOM 2906 OH2 TIP S 203 46.204 14.480 189.797 1.00 20.39 S ATOM 2907 OH2 TIP S 204 59.725 29.306 182.130 1.00 24.53 S ATOM 2908 OH2 TIP S 205 19.660 22.585 191.338 1.00 20.78 S ATOM 2909 OH2 TIP S 206 20.366 29.151 188.684 1.00 24.25 S ATOM 2910 OH2 TIP S 207 18.552 29.962 175.953 1.00 24.46 S ATOM 2911 OH2 TIP S 208 40.246 13.296 196.148 1.00 27.69 S ATOM 2912 OH2 TIP S 209 39.384 9.796 177.359 1.00 30.25 S ATOM 2913 OH2 TIP S 210 42.901 12.306 195.542 1.00 25.85 S ATOM 2914 OH2 TIP S 211 46.745 48.676 159.158 1.00 28.61 S ATOM 2915 OH2 TIP S 212 25.057 24.931 169.591 1.00 35.99 S ATOM 2916 OH2 TIP S 213 51.729 21.198 183.094 1.00 38.05 S ATOM 2917 OH2 TIP S 214 54.190 46.635 189.239 1.00 26.46 S ATOM 2918 OH2 TIP S 215 41.358 15.872 178.575 1.00 28.40 S ATOM 2919 OH2 TIP S 216 30.758 5.815 183.937 1.00 30.68 S ATOM 2920 OH2 TIP S 217 44.499 17.166 181.580 1.00 45.83 S ATOM 2921 OH2 TIP S 218 50.193 16.047 191.422 1.00 25.35 S ATOM 2922 OH2 TIP S 219 18.578 26.839 189.735 1.00 35.25 S ATOM 2923 OH2 TIP S 220 30.442 32.389 203.918 1.00 33.23 S ATOM 2924 OH2 TIP S 221 48.189 12.146 182.335 1.00 27.32 S ATOM 2925 OH2 TIP S 222 22.870 19.047 182.621 1.00 26.54 S ATOM 2926 OH2 TIP S 223 15.038 20.644 185.432 1.00 35.64 S ATOM 2927 OH2 TIP S 224 19.574 30.830 191.004 1.00 36.66 S ATOM 2928 OH2 TIP S 225 25.386 23.543 159.436 1.00 32.20 S ATOM 2929 OH2 TIP S 226 35.762 27.555 167.952 1.00 39.91 S ATOM 2930 OH2 TIP S 227 56.362 24.244 183.451 1.00 30.98 S ATOM 2931 OH2 TIP S 228 43.983 43.413 198.979 1.00 35.86 S ATOM 2932 OH2 TIP S 229 58.148 27.235 182.659 1.00 25.52 S ATOM 2933 OH2 TIP S 230 57.231 38.376 191.705 1.00 29.97 S ATOM 2934 OH2 TIP S 231 20.438 25.071 190.325 1.00 27.05 S ATOM 2935 OH2 TIP S 232 49.374 23.256 186.582 1.00 32.24 S ATOM 2936 OH2 TIP S 233 31.653 47.356 197.435 1.00 39.51 S ATOM 2937 OH2 TIP S 234 32.871 26.291 206.215 1.00 41.69 S ATOM 2938 OH2 TIP S 235 56.963 48.017 166.922 1.00 41.33 S ATOM 2939 OH2 TIP S 236 55.551 36.207 192.111 1.00 35.03 S ATOM 2940 OH2 TIP S 237 39.593 45.654 179.152 1.00 45.66 S ATOM 2941 OH2 TIP S 238 54.494 25.491 180.488 1.00 32.50 S ATOM 2942 OH2 TIP S 239 22.686 42.000 174.825 1.00 34.96 S ATOM 2943 OH2 TIP S 240 30.458 42.567 198.012 1.00 42.30 S ATOM 2944 OH2 TIP S 241 32.588 20.101 199.129 1.00 40.13 S ATOM 2945 OH2 TIP S 242 36.814 6.726 188.574 1.00 30.03 S ATOM 2946 OH2 TIP S 243 31.557 14.729 198.380 1.00 36.65 S ATOM 2947 OH2 TIP S 244 61.873 24.000 188.309 1.00 46.44 S ATOM 2948 OH2 TIP S 245 19.147 23.741 187.058 1.00 41.94 S ATOM 2949 OH2 TIP S 246 33.080 28.203 167.770 1.00 40.37 S ATOM 2950 OH2 TIP S 247 33.047 26.649 171.502 1.00 29.73 S ATOM 2951 OH2 TIP S 248 61.443 33.660 174.498 1.00 37.78 S ATOM 2952 OH2 TIP S 249 22.270 31.262 170.291 1.00 32.69 S ATOM 2953 OH2 TIP S 250 45.722 39.480 203.974 1.00 41.52 S ATOM 2954 OH2 TIP S 251 51.506 37.660 196.901 1.00 38.39 S ATOM 2955 OH2 TIP S 252 58.939 25.420 162.339 1.00 38.51 S ATOM 2956 OH2 TIP S 253 27.598 43.470 199.877 1.00 40.65 S ATOM 2957 OH2 TIP S 254 31.256 8.994 180.108 1.00 36.78 S ATOM 2958 OH2 TIP S 255 21.276 41.879 185.920 1.00 34.18 S ATOM 2959 OH2 TIP S 256 19.869 38.072 188.104 1.00 36.71 S ATOM 2960 OH2 TIP S 257 62.029 36.228 175.092 1.00 40.06 S ATOM 2961 OH2 TIP S 258 51.861 21.808 178.461 1.00 44.11 S ATOM 2962 OH2 TIP S 259 32.933 42.026 192.309 1.00 40.66 S ATOM 2963 OH2 TIP S 260 40.922 46.243 202.382 1.00 47.61 S ATOM 2964 OH2 TIP S 261 54.008 34.812 195.671 1.00 38.51 S ATOM 2965 OH2 TIP S 262 31.023 12.231 197.309 1.00 36.92 S ATOM 2966 OH2 TIP S 263 46.934 46.192 175.930 1.00 35.59 S ATOM 2967 OH2 TIP S 264 51.061 24.166 201.555 1.00 41.56 S ATOM 2968 OH2 TIP S 265 19.412 32.509 175.612 1.00 39.41 S ATOM 2969 OH2 TIP S 266 22.420 33.009 166.350 1.00 38.16 S ATOM 2970 OH2 TIP S 267 45.672 24.498 208.627 1.00 42.67 S ATOM 2971 OH2 TIP S 268 45.405 47.077 173.230 1.00 35.95 S ATOM 2972 OH2 TIP S 269 28.182 36.091 146.589 1.00 35.22 S ATOM 2973 OH2 TIP S 270 58.022 37.298 163.226 1.00 32.86 S ATOM 2974 OH2 TIP S 271 49.386 49.478 192.687 1.00 35.65 S ATOM 2975 OH2 TIP S 272 27.643 18.836 166.258 1.00 45.49 S ATOM 2976 OH2 TIP S 273 46.091 39.730 197.476 1.00 36.53 S ATOM 2977 OH2 TIP S 274 52.146 35.742 201.214 1.00 36.20 S ATOM 2978 OH2 TIP S 275 48.834 44.782 174.633 1.00 40.19 S ATOM 2979 OH2 TIP S 276 51.922 25.202 180.996 1.00 45.09 S ATOM 2980 OH2 TIP S 277 30.932 23.368 155.743 1.00 32.13 S ATOM 2981 OH2 TIP S 278 18.988 40.249 185.025 1.00 39.74 S ATOM 2982 OH2 TIP S 279 34.632 9.705 203.624 1.00 43.63 S ATOM 2983 OH2 TIP S 280 42.646 41.610 193.545 1.00 33.68 S END 

1. A crystal of PKBβ having a tetragonal space group P2₁2₁2₁, and unit cell dimensions of a=44.94±0.5 Å, b=61.00±0.5 Å, c=131.32±0.5 Å.
 2. A crystal according to claim 1, having unit cell dimensions of a=44.94±0.2 Å, b=61.00±0.2 Å, c=131.32±0.2 Å.
 3. A crystal according to claim 1 or claim 2, having unit cell dimensions of a=44.94 Å, b=61.00 Å, c=131.32 Å.
 4. A crystal according to any of claims 1 to 3 wherein the PKBβ comprises a mutation corresponding to the mutation S474D in human PKBβ.
 5. A crystal according to any of claims 1 to 3 wherein the PKBβ is a fusion protein having a C-terminal tail derived from another AGC kinase.
 6. A crystal according to claim 5 wherein the C-terminal tail comprises the sequence EEQEMFRDFDYIADW.
 7. A crystal according to any one of the preceding claims, wherein the PKBβ is co-complexed with one or more of a substrate peptide and a nucleotide or nucleotide analogue.
 8. A crystal of PKBβ having the three dimensional atomic coordinates of either of Tables 6 or
 7. 9. A method of determining the structure of a PKB derivative comprising the step of X-ray diffraction analysis of a crystal according to any one of the preceding claims.
 10. A method of analysing a PKBβ-ligand complex comprising the step of employing (i) X-ray crystallographic diffraction data from the PKBβ-ligand complex and (ii) a three-dimensional structure of PKBβ to generate a difference Fourier electron density map of the complex, the three-dimensional structure being defined by atomic coordinate data according to either of Tables 6 or
 7. 11. A method of determining a three dimensional structure for a target kinase comprising the steps of: (a) aligning a representation of an amino acid sequence of a target kinase of unknown structure with the amino acid sequence of PKBβ to match homologous regions of the amino acid sequences; (b) modelling the structure of the matched homologous regions of the target kinase on the structure of the corresponding regions of PKBβ as defined by either of Tables 6 or 7; and (c) determining a conformation for the target kinase which substantially preserves the structure of said matched homologous regions.
 12. A method for determining a three-dimensional structure for a target kinase, comprising the steps of; providing the co-ordinates of either of Tables 6 or 7, and positioning the co-ordinates in the crystal unit cell of said target kinase so as to provide a structure for said target kinase.
 13. A method according to claim 11 or claim 12, wherein the target kinase is an AGC kinase, or a co-complex, derivative or mutant thereof.
 14. A method according to claim 13, wherein the AGC kinase is PKBα or PKBγ, or a co-complex, derivative or mutant thereof.
 15. A computer system or computer-readable media containing either (a) atomic coordinate data of either of Tables 6 or 7, said data defining the three-dimensional structure of PKB, or at least selected coordinates thereof; (b) structure factor data for PKB, said structure factor data being derivable from the atomic coordinate data of either of Tables 6 or 7; (c) a Fourier transform of atomic coordinate data according to either of Tables 6 or 7, or at least selected coordinates thereof; (d) atomic coordinate data of a target kinase generated by homology modelling of the target based on the data of either of Tables 6 or 7; (e) atomic coordinate data of a target kinase generated by interpreting X-ray crystallographic data or NMR data by reference to the data of either of Tables 6 or 7; or (f) structure factor data derivable from the atomic coordinate data of (c), (d) or (e).
 16. A method for modelling the interaction between PKB and an agent compound which modulates PKB activity, comprising the steps of: (a) employing three-dimensional atomic coordinate data of either of Tables 6 or 7 to characterise at least one PKBβ binding site; (b) providing the structure of said agent compound; and (c) fitting said agent compound to the binding site.
 17. A method for identifying an agent compound which modulates PKB activity, comprising the steps of: (a) employing three-dimensional atomic coordinate data according to either of Tables 6 or 7 to characterise at least one PKBβ binding site; (b) providing the structure of a candidate agent compound; (c) fitting the candidate agent compound to the binding site; and (d) selecting the candidate agent compound.
 18. A method according to claim 17, wherein said binding site comprises all or part of the ATP binding site of PKBβ.
 19. A method according to claim 18, wherein said binding site comprises one or more amino acid residues corresponding to Val-166, Lys-181, Thr-213, Met-259, Ala-232, Glu-236, Lys-277, Glu-279, Met-282, Thr-292, Asp-293 of human PKBβ.
 20. A method according to claim 18 or claim 19, wherein said candidate agent compound is a better fit to the PKBβ binding site than to a corresponding binding site of PKA.
 21. A method according to claim 20, wherein binding of said candidate agent compound to said PKBβ binding site would be inhibited by one or more amino acid changes corresponding to mutations T213V, A232V and M282L of human PKBβ.
 22. A method according to claim 17, wherein said binding site comprises all or part of the substrate binding site of PKBβ.
 23. A method according to claim 22, wherein said binding site comprises one or more amino acid residues corresponding to Glu-279, Tyr-316, Glu-342, Glu-236, Glu-279, Phe-310, Cys-311 and Leu-317 of human PKBβ.
 24. A method according to claim 23, wherein when the candidate agent compound is fitted to the binding site, an interaction between said candidate agent compound and the binding site mimics an interaction between one or more of the following sets of residues of Tables 6 or 7: Arg-4 of GSK-3 and residues Glu-279, Tyr-316, Glu-342 of PKB-PIF; Arg-6 of GSK-3 and residues Glu-236, Glu-279 of PKB-PIF; Thr-7 of GSK-3 and residues Glu-279 of PKB-PIF; Phe-10 of GSK-3 and residues Phe-310, Cys-311, Leu-317 of PKB-PIF; Glu-12 of GSK-3 and residues Phe-310 of PKB-PIF.
 25. A method according to claim 17, wherein said binding site comprises all or part of the portion of the catalytic domain responsible for binding the C-terminal hydrophobic motif.
 26. A method according to claim 25, wherein said binding site comprises amino acid residues corresponding to one or more of the following amino acid residues of human PKBβ: Val-194, Gln-220, Ile-188, Ile-189, Val-198, Arg-202, Gln-205, Ser-201, Ala-218, Leu-225, Phe-227, Arg-208, Leu-215 and Lys-216.
 27. A method according to claim 26, wherein when the candidate agent compound is fitted to the binding site, an interaction between said candidate agent compound and the binding site mimics an interaction between one or more of the following sets of residues of PKB-PIF: Met-472 and Val-194, Gln-220; Phe-473 and Ile-188, Ile-189, Val-194, Val-198; Asp-475 and Arg-202, Gln-205; Phe-476 and Ser-201, Ala-218, Leu-225, Phe-227; Asp-477 and Gln-220; Tyr-478 and Arg-208, Leu-215; Ala-480 and Lys-216; Asp-481 and Arg-208; Trp-479 and Leu-215, Lys-216.
 28. A method according to any one of claims 17 to 27 wherein: a plurality of binding sites are characterised and a plurality of agent compounds are fitted to said sites; and said agent compounds are linked to form a potential modulator compound.
 29. A method according to any one of claims 17 to 28 wherein step (b) comprises selecting said candidate agent compound by computationally screening a database of compounds for interaction with said binding site.
 30. A method according to any one of claims 17 to 29 which comprises the further steps of: (e) obtaining or synthesising the candidate agent compound; and (f) contacting the candidate agent compound with PKB to determine the ability of the candidate agent compound to interact with PKB.
 31. A method according to any one of claims 17 to 29 which comprises the further steps of: (e) obtaining or synthesising the candidate agent compound; (f) forming a complex of PKB and the candidate agent compound; and (g) analysing said complex by X-ray crystallography or NMR spectroscopy to determine the ability of the candidate agent compound to interact with PKB.
 32. A compound which is identified as a modulator of PKB activity by the method of any one of claims 17 to
 31. 